SMPD1 gene
cDNA Reference Sequence NM_000543.4
Protein accession number NP_000534.3
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Found in NPA/B Patients
c.-162G>A
NA
Domain: Type: Intronic variant SIFT: MAF: A=0.0002/1
Composite Position: 11:6390437 Found in NPA/B patients: No PolyPhen:
Exon/Intron: utr-5 Found in Controls: Yes Reference:
rs ID: rs113418824 Predicted effect: Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.-133C>T
NA
Domain: Type: Intronic variant SIFT: MAF: T=0.0006/3
Composite Position: 11:6390466 Found in NPA/B patients: No PolyPhen:
Exon/Intron: utr-5 Found in Controls: Yes Reference:
rs ID: rs372965365 Predicted effect: Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.-132G>A
NA
Domain: Type: Intronic variant SIFT: MAF: A=0.0070/35
Composite Position: 11:6390467 Found in NPA/B patients: No PolyPhen:
Exon/Intron: utr-5 Found in Controls: Yes Reference:
rs ID: rs114874902 Predicted effect: Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.-98C>T
NA
Domain: Type: Intronic variant SIFT: MAF: T=0.0002/1
Composite Position: 11:6390501 Found in NPA/B patients: No PolyPhen:
Exon/Intron: utr-5 Found in Controls: Yes Reference:
rs ID: rs147605872 Predicted effect: Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.-97G>T
NA
Domain: Type: Intronic variant SIFT: MAF: T=0.0008/3
Composite Position: 11:6390502 Found in NPA/B patients: No PolyPhen:
Exon/Intron: utr-5 Found in Controls: Yes Reference:
rs ID: rs563116210 Predicted effect: Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.-78C>T
NA
Domain: Type: Intronic variant SIFT: MAF: T=0.0002/1
Composite Position: 11:6390521 Found in NPA/B patients: No PolyPhen:
Exon/Intron: utr-5 Found in Controls: Yes Reference:
rs ID: rs533338773 Predicted effect: Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.-66G>A
NA
Domain: Type: Intronic variant SIFT: MAF: NA
Composite Position: 11:6390533 Found in NPA/B patients: No PolyPhen:
Exon/Intron: utr-5 Found in Controls: Yes Reference:
rs ID: rs374470369 Predicted effect: Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.-50G>A
NA
Domain: Type: Intronic variant SIFT: MAF: A=0.000/1
Composite Position: 11:6390549 Found in NPA/B patients: No PolyPhen:
Exon/Intron: utr-5 Found in Controls: Yes Reference:
rs ID: rs200242748 Predicted effect: Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.-45G>C
NA
Domain: Type: Intronic variant SIFT: MAF: C=0.0196/98
Composite Position: 11:6390554 Found in NPA/B patients: No PolyPhen:
Exon/Intron: utr-5 Found in Controls: Yes Reference:
rs ID: rs79282481 Predicted effect: Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.-35G>T
NA
Domain: Type: Intronic variant SIFT: MAF: T=0.0002/1
Composite Position: 11:6390564 Found in NPA/B patients: No PolyPhen:
Exon/Intron: utr-5 Found in Controls: Yes Reference:
rs ID: rs375247947 Predicted effect: Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.-28C>G
NA
Domain: Type: Intronic variant SIFT: MAF: C=0.0002/1
Composite Position: 11:6390571 Found in NPA/B patients: No PolyPhen:
Exon/Intron: utr-5 Found in Controls: Yes Reference:
rs ID: rs549375319 Predicted effect: Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.-12G>A
NA
Domain: Type: Intronic variant SIFT: MAF: NA
Composite Position: 11:6390587 Found in NPA/B patients: No PolyPhen:
Exon/Intron: utr-5 Found in Controls: Yes Reference:
rs ID: rs375787350 Predicted effect: Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.2T>G
p.M1_W32del
Domain: Signal Peptide Type: In frame deletion SIFT: MAF: NA
Composite Position: 11:6390600 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 1 Found in Controls: No Reference: Pittis et al., 2004
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies: In vitro expression in COS-1 cells. Less than 5% of residual ASM activity compared to wild-type ASM (Dardis et al., 2005).
c.4delC
p.R3Afs*76
Domain: Signal Peptide Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6390602 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 1 Found in Controls: No Reference: Zhang et al., 2013
rs ID: rs281860663 Predicted effect: Probably pathogenic Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.8G>A
p.R3H
Domain: Signal Peptide Type: Missense SIFT: Tolerated (0.37) MAF: A=0.0006/3
Composite Position: 11:6390606 Found in NPA/B patients: No PolyPhen: benign:0.007
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs199836262 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.26G>T
p.R9L
Domain: Signal Peptide Type: Missense SIFT: Tolerated (0.22) MAF: NA
Composite Position: 11:6390624 Found in NPA/B patients: No PolyPhen: benign:0.022
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs373013062 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.40A>G
p.R14G
Domain: Signal Peptide Type: Missense SIFT: Tolerated (0.14) MAF: NA
Composite Position: 11:6390638 Found in NPA/B patients: No PolyPhen: benign:0.000
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs11544727 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.56A>G
p.Q19R
Domain: Signal Peptide Type: Missense SIFT: Tolerated (0.49) MAF: NA
Composite Position: 11:6390654 Found in NPA/B patients: No PolyPhen: benign:0.000
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs144465428 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.58G>A
p.G20R
Domain: Signal Peptide Type: Missense SIFT: Tolerated (0.74) MAF: A=0.0002/1
Composite Position: 11:6390656 Found in NPA/B patients: No PolyPhen: benign:0.000
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs538153468 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.61C>T
p.Q21X
Domain: Signal Peptide Type: Nonsense SIFT: MAF: NA
Composite Position: 11:6390659 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 1 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.71_73delCCG
p.A25del
Domain: Signal Peptide Type: In frame deletion SIFT: MAF: NA
Composite Position: 11:6390668_6390670 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: unknown Predicted effect: Unknown significance Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.84C>G
p.(=)
Domain: Signal Peptide Type: Synonymous codon SIFT: MAF: G=0.0002/1
Composite Position: 11:6390682 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs577769499 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.84delC
p.G29Dfs*48
Domain: Signal Peptide Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6390682 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 1 Found in Controls: No Reference: Sikora et al., 2003
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.88C>T
p.L30F
Domain: Signal Peptide Type: Missense SIFT: Tolerated (0.22) MAF: NA
Composite Position: 11:6390686 Found in NPA/B patients: No PolyPhen: possibly-damaging:0.662
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs376159116 Predicted effect: Unknown significance Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.96G>A
p.W32X
Domain: Signal Peptide Type: Nonsense SIFT: MAF: NA
Composite Position: 11:6390694 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 1 Found in Controls: No Reference: Pittis et al., 2004
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies: In vitro expression in COS-1 cells. Less than 5% of residual ASM activity compared to wild-type ASM (Dardis et al., 2005).
c.99G>A
p.M33I
Domain: Signal Peptide Type: Missense SIFT: Tolerated (0.18) MAF: A=0.0038/19
Composite Position: 11:6390697 Found in NPA/B patients: No PolyPhen: benign:0.0
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs142178073 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.100delG
p.G34Afs*43
Domain: Signal Peptide Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6390698 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 1 Found in Controls: No Reference: Pittis et al., 2004
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies: In vitro expression in COS-1 cells. Less than 5% of residual ASM activity compared to wild-type ASM (Dardis et al., 2005).
c.103C>G
p.L35V
Domain: Signal Peptide Type: Missense SIFT: Tolerated (0.54) MAF: NA
Composite Position: 11:6390701 Found in NPA/B patients: No PolyPhen: benign:0.058
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs201367689 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.103_126del24
p.V36_L43del
Domain: Signal Peptide Type: In frame deletion SIFT: MAF: -=0.0010/5
Composite Position: 11:6390701_6390724 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs550067660 Predicted effect: Unknown significance Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.106G>T
p.V36L
Domain: Signal Peptide Type: Missense SIFT: Tolerated (1.00) MAF: NA
Composite Position: 11:6390704 Found in NPA/B patients: No PolyPhen: benign:0.017
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs141685473 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.107T>C
p.V36A
Domain: Signal Peptide Type: Missense SIFT: Tolerated (0.12) MAF: T=0.4387/2196
Composite Position: 11:6390705 Found in NPA/B patients: Yes PolyPhen: benign:0.0
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs1050228 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies: Polymorphism
c.107_108insCTGGC
p.L37Wfs*42
Domain: Signal Peptide Type: Frameshift SIFT: MAF:
Composite Position: 11:6390705_6390706 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 1 Found in Controls: No Reference: Wittmann et al., 2012
rs ID: Unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.107_118delTGCTGGCGCTGG
p.V36_L39del
Domain: Signal Peptide Type: In frame deletion SIFT: MAF: -=0.0351/176
Composite Position: 11:6390705_6390716 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs550365194 Predicted effect: Unknown significance Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.108G>C
p.(=)
Domain: Signal Peptide Type: Synonymous codon SIFT: MAF: NA
Composite Position: 11:6390706 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs61729852 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.108_113[3_6]
p.L37_A38[3_8]
Domain: Signal Peptide Type: Duplication SIFT: MAF: NA
Composite Position: 11:6390706_6390711 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 1 Found in Controls: Yes Reference: Wan and Schuchmann 1995
rs ID: rs3838786 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies: Polymorphism
c.113C>T
p.A38V
Domain: Signal Peptide Type: Missense SIFT: Tolerated (0.61) MAF: NA
Composite Position: 11:6390711 Found in NPA/B patients: No PolyPhen: benign:0.004
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs78250081 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.119C>T
p.A40V
Domain: Signal Peptide Type: Missense SIFT: Tolerated (0.29) MAF: NA
Composite Position: 11:6390717 Found in NPA/B patients: No PolyPhen: benign:0.005
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs377374691 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.125C>T
p.A42V
Domain: Signal Peptide Type: Missense SIFT: Tolerated (0.22) MAF: NA
Composite Position: 11:6390723 Found in NPA/B patients: No PolyPhen: benign:0.0
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs200577287 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.126G>T
p.(=)
Domain: Signal Peptide Type: Synonymous codon SIFT: MAF: T=0.0262/130
Composite Position: 11:6390724 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs571806745 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.135G>T
p.(=)
Domain: Signal Peptide Type: Synonymous codon SIFT: MAF: NA
Composite Position: 11:6390733 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs150867628 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.138G>T
p.(=)
Domain: Signal Peptide Type: Synonymous codon SIFT: MAF: NA
Composite Position: 11:6390736 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs200763765 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.147_150delGTCT
p.S50Tfs*26
Domain: Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6390745_6390748 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 1 Found in Controls: No Reference: Zhang et al., 2013
rs ID: rs281860676 Predicted effect: Probably pathogenic Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.152A>T
p.D51V
Domain: Type: Missense SIFT: Tolerated (0.16) MAF: NA
Composite Position: 11:63907450 Found in NPA/B patients: Yes PolyPhen: possibly damaging (0.773)
Exon/Intron: exon 1 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: Unknown Predicted effect: Unknown significance Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.151_154delGACT
p.D51Lfs*25
Domain: Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6390749_6390752 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 1 Found in Controls: No Reference: Lidove et al., 2015
rs ID: Unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.162T>C
p.(=)
Domain: Type: Synonymous codon SIFT: MAF: NA
Composite Position: 11:6390760 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs375248757 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.169delG
p.A57Lfs*20
Domain: Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6390767 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 1 Found in Controls: No Reference: Irun et al., 2012
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.174G>A
p.(=)
Domain: Type: Synonymous codon SIFT: MAF: NA
Composite Position: 11:6390772 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs368143181 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.177A>G
p.(=)
Domain: Type: Synonymous codon SIFT: MAF: G=0.0002/1
Composite Position: 11:6390775 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs199586053 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.196C>T
p.P66S
Domain: Type: Missense SIFT: Tolerated (0.81) MAF: NA
Composite Position: 11:6390794 Found in NPA/B patients: No PolyPhen: benign:0.0
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs139716279 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.201A>T
p.Q67H
Domain: Type: Missense SIFT: Tolerated (0.21) MAF: NA
Composite Position: 11:6390799 Found in NPA/B patients: No PolyPhen: benign:0.001
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs11544728 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.211G>A
p.A71T
Domain: Type: Missense SIFT: Tolerated (0.37) MAF: NA
Composite Position: 11:6390809 Found in NPA/B patients: No PolyPhen: benign:0.137
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs375224040 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.229G>A
p.V77M
Domain: Type: Missense SIFT: Tolerated (0.23) MAF: A=0.0010/5
Composite Position: 11:6390827 Found in NPA/B patients: No PolyPhen: benign:0.065
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs560531338 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.234C>T
p.(=)
Domain: Type: Synonymous codon SIFT: MAF: T=0.0002/1
Composite Position: 11:6390832 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs575601110 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.236G>A
p.R79Q
Domain: Type: Missense SIFT: Tolerated (0.72) MAF: A=0.0002/1
Composite Position: 11:6390834 Found in NPA/B patients: No PolyPhen: benign:0.0
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs201647015 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.253G>A
p.G85R
Domain: Type: Missense SIFT: Tolerated (0.65) MAF: A=0.0020/10
Composite Position: 11:6390851 Found in NPA/B patients: No PolyPhen: possibly damaging (0.809)
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs368200803 Predicted effect: Unknown significance Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.258G>A
p.W86X
Domain: Type: Nonsense SIFT: MAF: NA
Composite Position: 11:6390856 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 1 Found in Controls: No Reference: This article
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.271_272delTGinsCA
p.C91H
Domain: Saposin B domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6390869_6390870 Found in NPA/B patients: Yes PolyPhen: possibly damaging (1.00)
Exon/Intron: exon 1 Found in Controls: No Reference: Hollack et al., 2012
rs ID: Unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.282C>G
p.C94W
Domain: Saposin B domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6390880 Found in NPA/B patients: Yes PolyPhen: possibly damaging (1.00)
Exon/Intron: exon 1 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.291A>G
p.(=)
Domain: Saposin B domain Type: Synonymous codon SIFT: MAF: G=0.0002/1
Composite Position: 11:6390889 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs144428799 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.297C>G
p.(=)
Domain: Saposin B domain Type: Synonymous codon SIFT: MAF: G=0.0002/1
Composite Position: 11:6390895 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs146630228 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.301A>G
p.I101V
Domain: Saposin B domain Type: Missense SIFT: Tolerated (0.31) MAF: NA
Composite Position: 11:6390899 Found in NPA/B patients: No PolyPhen: benign:0.002
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs369746362 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.305A>G
p.N102S
Domain: Saposin B domain Type: Missense SIFT: Tolerated (0.75) MAF: G=0.0004/1
Composite Position: 11:6390903 Found in NPA/B patients: No PolyPhen: benign:0.003
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs373475928 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.310G>A
p.G104R
Domain: Saposin B domain Type: Missense SIFT: Tolerated (0.42) MAF: A=0.0004/1
Composite Position: 11:6390908 Found in NPA/B patients: No PolyPhen: possibly damaging (0.797)
Exon/Intron: exon 1 Found in Controls: Yes Reference:
rs ID: rs527767942 Predicted effect: Unknown significance Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.314T>C
p.L105P
Domain: Saposin B domain Type: Missense SIFT: Damaging (0.04) MAF: NA
Composite Position: 11:6390912 Found in NPA/B patients: Yes PolyPhen: possibly damaging (0.998)
Exon/Intron: exon 1 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies: In vitro expression in COS-1 cells. Less than 5% of residual ASM activity compared to wild-type ASM (Dardis et al., 2005).
c.318+1G>T
NA
Domain: Type: Intronic variant SIFT: MAF: NA
Composite Position: 11:6390917 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: intron 1 Found in Controls: No Reference: Irun et al., 2012
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note: In silico analysis. NNsplice WT 5': 1.00 MUT 5': ND; Sroogle _G WT 5': -7.30 MUT 5':ND; MES WT 5': 9.66 MUT 5': ND; Senepathy WT 5': 88.91 MUT 5':ND.
Functional studies:
c.318+5G>A
NA
Domain: Type: Intronic variant SIFT: MAF: NA
Composite Position: 11:6390921 Found in NPA/B patients: No PolyPhen:
Exon/Intron: intron 1 Found in Controls: Yes Reference:
rs ID: rs375723261 Predicted effect: Probably pathogenic Ref Link: http://evs.gs.washington.edu/EVS/
Curator note: In silico analysis. NNsplice WT 5': 1.00 MUT 5': 0.33; Sroogle _G WT 5': -7.30 MUT 5': -5.30; MES WT 5': 9.66 MUT 5': 5.54; Senepathy WT 5': 88.91 MUT 5': 77.19.
Functional studies:
c.318+10G>C
NA
Domain: Type: Intronic variant SIFT: MAF: NA
Composite Position: 11:6390926 Found in NPA/B patients: No PolyPhen:
Exon/Intron: intron 1 Found in Controls: Yes Reference:
rs ID: rs367666720 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.318+21A>G
NA
Domain: Type: Intronic variant SIFT: MAF: NA
Composite Position: 11:6390937 Found in NPA/B patients: No PolyPhen:
Exon/Intron: intron 1 Found in Controls: Yes Reference:
rs ID: rs372368356 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.318+49G>C
NA
Domain: Type: Intronic variant SIFT: MAF: C=0.0004/1
Composite Position: 11:6390965 Found in NPA/B patients: No PolyPhen:
Exon/Intron: intron 1 Found in Controls: Yes Reference:
rs ID: rs377095028 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.319-40T>C
NA
Domain: Type: Intronic variant SIFT: MAF: NA
Composite Position: 11:6391344 Found in NPA/B patients: No PolyPhen:
Exon/Intron: intron 1 Found in Controls: Yes Reference:
rs ID: rs375429408 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note: In silico analysis. No difference between WT and mutant sequence scores.
Functional studies:
c.319-33C>G
NA
Domain: Type: Intronic variant SIFT: MAF: G=0.0002/1
Composite Position: 11:6391351 Found in NPA/B patients: No PolyPhen:
Exon/Intron: intron 1 Found in Controls: Yes Reference:
rs ID: rs143462566 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note: In silico analysis. NNsplice: no change; Sroogle Branch site (Kol and Schwartz) no change; Polypyrimidine tract (Kol) no change; Polypyrimidine tract (Schwartz) WT 3': 12.46 MUT 3': 9.00; MES no change; PSSM no change.
Functional studies:
c.319-24C>T
NA
Domain: Type: Intronic variant SIFT: MAF: T=0.0010/5
Composite Position: 11:6391360 Found in NPA/B patients: No PolyPhen:
Exon/Intron: intron 1 Found in Controls: Yes Reference:
rs ID: rs560680564 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note: In silico analysis. No difference between WT and mutant sequence scores.
Functional studies:
c.319-17C>A
NA
Domain: Type: Intronic variant SIFT: MAF: A=0.0002/1
Composite Position: 11:6391367 Found in NPA/B patients: No PolyPhen:
Exon/Intron: intron 1 Found in Controls: Yes Reference:
rs ID: rs148370501 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note: In silico analysis. NNsplice WT 3': 0.84 MUT 3': 0.81; Sroogle Branch site (Kol and Schwartz) no change; Polypyrimidine tract (Kol and Schwartz) no change; MES WT 3': 7.88 MUT 3': 6.80; PSSM WT 3': 83.73 MUT 3': 82.66.
Functional studies:
c.336T>C
p.(=)
Domain: Saposin B domain Type: Synonymous codon SIFT: MAF: C=0.0004/1
Composite Position: 11:6391401 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs543145636 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.337C>T
p.R113C
Domain: Saposin B domain Type: Missense SIFT: Damaging (0.04) MAF: T=0.0008/3
Composite Position: 11:6391402 Found in NPA/B patients: No PolyPhen: Benign:0.032
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs140202512 Predicted effect: Unknown significance Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.338G>A
p.R113H
Domain: Saposin B domain Type: Missense SIFT: Tolerated (0.1) MAF: A=0.0010/5
Composite Position: 11:6391403 Found in NPA/B patients: No PolyPhen: Benign:0.014
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs149770879 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.340G>A
p.V114M
Domain: Saposin B domain Type: Missense SIFT: Tolerated (0.14) MAF: A=0.0006/3
Composite Position: 11:6391405 Found in NPA/B patients: Yes PolyPhen: probably-damaging:0.992
Exon/Intron: exon 2 Found in Controls: Yes Reference: Gucev et al., 2013
rs ID: rs142215226 Predicted effect: Unknown significance Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.343G>A
p.G115S
Domain: Saposin B domain Type: Missense SIFT: Tolerated (0.42) MAF: A=0.0002/1
Composite Position: 11:6391408 Found in NPA/B patients: No PolyPhen: benign:0.232
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs199913218 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.349G>A
p.V117M
Domain: Saposin B domain Type: Missense SIFT: Tolerated (0.64) MAF: A=0.0002/1
Composite Position: 11:6391414 Found in NPA/B patients: No PolyPhen: Benign:0.032
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs202206564 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.353delC
p.I119Sfs*7
Domain: Saposin B domain Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6391418 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.373C>T
p.(=)
Domain: Saposin B domain Type: Synonymous codon SIFT: MAF: NA
Composite Position: 11:6391438 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs370048730 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.390T>G
p.(=)
Domain: Saposin B domain Type: Synonymous codon SIFT: MAF: NA
Composite Position: 11:6391455 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs371141815 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.394G>A
p.V132M
Domain: Saposin B domain Type: Missense SIFT: Damaging (0) MAF: A=0.0002/1
Composite Position: 11:6391459 Found in NPA/B patients: No PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs189859589 Predicted effect: Probably pathogenic Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.395T>C
p.V132A
Domain: Saposin B domain Type: Missense SIFT: Damaging (0.01) MAF: NA
Composite Position: 11:6391460 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Dardis et al., 2005
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies: In vitro expression in COS-1 cells. 13% of residual ASM activity compared to wild-type ASM (Dardis et al., 2005). In vitro expression in COS-7 cells. 33% of residual ASM activity compared to wild-type ASM (Rodriguez-Pascau et al., 2009).
c.406A>G
p.I136V
Domain: Saposin B domain Type: Missense SIFT: Tolerated (0.64) MAF: NA
Composite Position: 11:6391471 Found in NPA/B patients: No PolyPhen: Benign:0.057
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs556385880 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.416C>T
p.L139P
Domain: Saposin B domain Type: Missense SIFT: Damaging (0.04) MAF: NA
Composite Position: 11:6391481 Found in NPA/B patients: Yes PolyPhen: probably-damaging:0.998
Exon/Intron: exon 2 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.431_433delTGG
p.V145del
Domain: Saposin B domain Type: In frame deletion SIFT: MAF: NA
Composite Position: 11:6391495_6391497 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: unknown Predicted effect: Unknown significance Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.441G>A
p.(=)
Domain: Saposin B domain Type: Synonymous codon SIFT: MAF: A=0.0034/17
Composite Position: 11:6391506 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs148944108 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.448C>T
p.R150C
Domain: Saposin B domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6391513 Found in NPA/B patients: No PolyPhen: probably-damaging:0.997
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs143719170 Predicted effect: Probably pathogenic Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.472G>A
p.A158T
Domain: Saposin B domain Type: Missense SIFT: Damaging (0.02) MAF: NA
Composite Position: 11:6391537 Found in NPA/B patients: No PolyPhen: probably-damaging:0.964
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs369566518 Predicted effect: Probably pathogenic Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.475C>T
p.C159R
Domain: Saposin B domain Type: Missense SIFT: Damaging (0.01) MAF: NA
Composite Position: 11:6391540 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Ida et al., 1993
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.488T>C
p.L163P
Domain: Saposin B domain Type: Missense SIFT: Tolerated (0.25) MAF: NA
Composite Position: 11:6391553 Found in NPA/B patients: Yes PolyPhen: probably-damaging:0.996
Exon/Intron: exon 2 Found in Controls: No Reference: Meerseman et al., 2011
rs ID: unknown Predicted effect: Unknown significance Ref Link:
Curator note:
Functional studies:
c.502G>A
p.G168R
Domain: Proline rich domain Type: Missense SIFT: Tolerated (0.28) MAF: NA
Composite Position: 11:6391567 Found in NPA/B patients: Yes PolyPhen: probably-damaging:0.970
Exon/Intron: exon 2 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Unknown significance Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.509G>A
p.W170X
Domain: Proline rich domain Type: Nonsense SIFT: MAF: NA
Composite Position: 11:6391574 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Rodr?guez-Pascau et al., 2009
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.511delG
D170Tfs*86
Domain: Proline rich domain Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6391576 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.518dupT
p.S174Lfs*19
Domain: Proline rich domain Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6391583 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Ricci et al., 2004
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.523T>C
p.S175P
Domain: Proline rich domain Type: Missense SIFT: Tolerated (0.14) MAF: NA
Composite Position: 11:6391588 Found in NPA/B patients: No PolyPhen: benign:0.002
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs147607780 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.528C>A
p.W176X
Domain: Proline rich domain Type: Nonsense SIFT: MAF: NA
Composite Position: 11:6391593 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.533T>A
p.I178N
Domain: Proline rich domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6391598 Found in NPA/B patients: Yes PolyPhen: probably-damaging:0.992
Exon/Intron: exon 2 Found in Controls: No Reference: M?ssig K et al., 2006
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.534C>T
p.(=)
Domain: Proline rich domain Type: Synonymous codon SIFT: MAF: NA
Composite Position: 11:6391599 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs142147633 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.538_539delTT
p.L180Afs*12
Domain: Proline rich domain Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6391603_6391604 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Takahashi et al., 1992
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies: In vitro expression in COS-1 cells. Less than 5% of residual ASM activity compared to wild-type ASM (Takahashi et al., 1992).
c.557C>T
p.P186L
Domain: Proline rich domain Type: Missense SIFT: Damaging (0.02) MAF: NA
Composite Position: 11:6391622 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Pavl_-Pereira et al., 2005
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies: In vitro expression in ASM-deficient fibroblasts. 43% of residual ASM activity compared to wild-type ASM (Pavlu-Pereira et al., 2005).
c.559C>T
p.P187S
Domain: Proline rich domain Type: Missense SIFT: Tolerated (0.19) MAF: T=0.0164/82
Composite Position: 11:6391624 Found in NPA/B patients: No PolyPhen: benign:0.1
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs74053349 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.564_565insA
p.P190Tfs*3
Domain: Proline rich domain Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6391629 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.572dupC
p.S192fs*1
Domain: Proline rich domain Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6391637 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Pittis et al., 2004
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies: In vitro expression in COS-1 cells. Less than 5% of residual ASM activity compared to wild-type ASM (Dardis et al., 2005).
c.573delT
p.S192Afs*65
Domain: Proline rich domain Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6391638 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Gluck et al., 1998
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.573_575delTAG
p.S192del
Domain: Proline rich domain Type: In frame deletion SIFT: MAF: NA
Composite Position: 11:6391638_6391640 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: unknown Predicted effect: Unknown significance Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.581dupC
p.A195Sfs*14
Domain: Proline rich domain Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6391646 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Pittis et al., 2004
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies: In vitro expression in COS-1 cells. Less than 5% of residual ASM activity compared to wild-type ASM (Dardis et al., 2005).
c.581delC
p.P194Qfs*63
Domain: Proline rich domain Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6391646 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Ricci et al., 2004
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.592G>T
p.A198P
Domain: Proline rich domain Type: Missense SIFT: Tolerated (0.2) MAF: NA
Composite Position: 11:6391657 Found in NPA/B patients: Yes PolyPhen: probably-damaging:0.831
Exon/Intron: exon 2 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Unknown significance Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.604C>T
p.R202C
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6391669 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.627G>C
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: C=0.0002/1
Composite Position: 11:6391692 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs200443318 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.631T>C
p.W211R
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0.01) MAF: NA
Composite Position: 11:6391696 Found in NPA/B patients: Yes PolyPhen: probably-damaging:0.997
Exon/Intron: exon 2 Found in Controls: No Reference: Desnick et al., 2010
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies: In vitro expression in 293-T cells. Less than 5% of residual ASM activity compared to wild-type ASM (Desnick et al., 2010).
c.636T>C
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: C=0.1282/642
Composite Position: 11:6391701 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs7951904 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.657G>A
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: A=0.0002/1
Composite Position: 11:6391722 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs202032347 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.679C>A
p.L227M
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.23) MAF: NA
Composite Position: 11:6391744 Found in NPA/B patients: Yes PolyPhen: probably-damaging:0.994
Exon/Intron: exon 2 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Unknown significance Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.680T>C
p.L227P
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6391745 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Pittis et al., 2004
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies: In vitro expression in COS-1 cells. Less than 5% of residual ASM activity compared to wild-type ASM (Dardis et al., 2005).
c.682T>C
p.C228R
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6391747 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Irun et al., 2012
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.688C>T
p.R230C
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6391753 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies: In vitro expression in COS-7 cells. Less than 5% of residual ASM activity compared to wild-type ASM (Rodriguez-Pascau et al., 2009).
c.689G>A
p.R230H
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: A=0.0002/1
Composite Position: 11:6391754 Found in NPA/B patients: Yes PolyPhen: probably-damaging:0.996
Exon/Intron: exon 2 Found in Controls: No Reference: Pavl_-Pereira et al., 2005
rs ID: rs141387770 Predicted effect: Probably pathogenic Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.689G>A;c.1805G>A
p.R230H;p.R602H
Domain: C- terminal domain , phosphoesterase domain Type: 2 changes in one allele SIFT: MAF: NA
Composite Position: 11:6391754;11:6394516 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 , exon 6 Found in Controls: No Reference: This article
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.691C>A
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: A=0.0002/1
Composite Position: 11:6391756 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs199832734 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.701G>A
p.G234D
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.06) MAF: NA
Composite Position: 11:6391766 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Unknown significance Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.708G>A
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: NA
Composite Position: 11:6391773 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs374604948 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.714A>G
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: G=0.0280/140
Composite Position: 11:6391779 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs2682091 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.719G>A
p.R240Q
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.6) MAF: A=0.0056/2
Composite Position: 11:6391784 Found in NPA/B patients: No PolyPhen: benign:0
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs2634197 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.728C>T
p.A243V
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6391793 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Pavl_-Pereira et al., 2005
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.729C>T
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: NA
Composite Position: 11:6391794 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs149476159 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.730G>A
p.G244R
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6391795 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Takahashi et al., 1992
rs ID: rs120074122 Predicted effect: Probably pathogenic Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies: In vitro expression in COS-1 cells. 40% of residual ASM activity compared to wild-type ASM (Takahashi et al., 1992).
c.733T>C
p.Y245H
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.35) MAF: NA
Composite Position: 11:6391798 Found in NPA/B patients: No PolyPhen: benign:0.081
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs370178721 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.738G>C
p.W246C
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6391803 Found in NPA/B patients: Yes PolyPhen: probably-damaging:0.991
Exon/Intron: exon 2 Found in Controls: No Reference: Pittis et al., 2004
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies: In vitro expression in COS-1 cells. Less than 5% of residual ASM activity compared to wild-type ASM (Dardis et al., 2005).
c.739G>A
p.G247S
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.16) MAF: NA
Composite Position: 11:6391804 Found in NPA/B patients: Yes PolyPhen: probably-damaging:0.920
Exon/Intron: exon 2 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Unknown significance Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.740G>A
p.G247D
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6391805 Found in NPA/B patients: Yes PolyPhen: probably-damaging:0.999
Exon/Intron: exon 2 Found in Controls: No Reference: Toth et al., 2012
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies: In vitro expression in COS-7 cells. Less than 5% of residual ASM activity compared to wild-type ASM (Toth et al., 2011).
c.740delG
p.G247Afs*9
Domain: phosphoesterase domain Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6391805 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Galehdari et al., 2013
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.741_742delinsGC
p.E248Q
Domain: phosphoesterase domain Type: Indel SIFT: Damaging (0.01) MAF: NA
Composite Position: 11:6391806_6391807 Found in NPA/B patients: Yes PolyPhen: probably-damaging:0.976
Exon/Intron: exon 2 Found in Controls: No Reference: Ida et al., 1996
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies: In vitro expression in COS-7 cells. 30% of residual ASM activity compared to wild-type ASM (Ida et al., 1996).
c.742G>A
p.E248K
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0.01) MAF: NA
Composite Position: 11:6391807 Found in NPA/B patients: Yes PolyPhen: probably-damaging:0.947
Exon/Intron: exon 2 Found in Controls: No Reference: Ricci et al., 2004
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.742G>T
p.E248X
Domain: phosphoesterase domain Type: Nonsense SIFT: MAF: NA
Composite Position: 11:6391807 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Zhang et al., 2013
rs ID: rs200763423 Predicted effect: Probably pathogenic Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.742G>T;c.1445T>C
p.E248X; p.F482S
Domain: C- terminal domain , phosphoesterase domain Type: 2 changes in one allele SIFT: MAF: NA
Composite Position: 11:6391807;11:6394000 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 , exon 5 Found in Controls: No Reference: Zhang et al., 2013
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.748A>C
p.S250R
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (1) MAF: NA
Composite Position: 11:6391813 Found in NPA/B patients: Yes PolyPhen: benign:0.004
Exon/Intron: exon 2 Found in Controls: No Reference: Sikora et al., 2003
rs ID: unknown Predicted effect: Unknown significance Ref Link:
Curator note:
Functional studies:
c.748A>C;c.1411G>A
p.S250R; p.E471K
Domain: C- terminal domain , phosphoesterase domain Type: 2 changes in one allele SIFT: MAF: NA
Composite Position: 11:6391813;11:6393966 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 , exon 5 Found in Controls: No Reference: Zhang et al., 2013
rs ID: unknown Predicted effect: Unknown significance Ref Link:
Curator note:
Functional studies:
c.750C>A
p.S250R
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (1) MAF: NA
Composite Position: 11:6391815 Found in NPA/B patients: Yes PolyPhen: benign:0.004
Exon/Intron: exon 2 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Unknown significance Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.753G>A
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: NA
Composite Position: 11:6391818 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs374458858 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.757G>C
p.D253H
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6391822 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Desnick et al., 2010
rs ID: rs398123479 Predicted effect: Probably pathogenic Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies: In vitro expression in 293-T cells. Less than 5% of residual ASM activity compared to wild-type ASM (Desnick et al., 2010).
c.759C>A
p.D253E
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6391824 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Pavl_-Pereira et al., 2005
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies: In vitro expression in ASM-deficient fibroblasts. 40% of residual ASM activity compared to wild-type ASM (Pavl_-Pereira et al., 2005).
c.762G>A
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: A=0.0016/7
Composite Position: 11:6391827 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs143939609 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.767T>C
p.L256P
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.238) MAF: C=0.0002/1
Composite Position: 11:6391832 Found in NPA/B patients: No PolyPhen: probably-damaging:0.732
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs139882665 Predicted effect: Unknown significance Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.773C>T
p.T258I
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0.04) MAF: NA
Composite Position: 11:6391838 Found in NPA/B patients: Yes PolyPhen: probably-damaging:0.999
Exon/Intron: exon 2 Found in Controls: No Reference: This article
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.778G>T
p.E260X
Domain: phosphoesterase domain Type: Nonsense SIFT: MAF: NA
Composite Position: 11:6391843 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: ida et al., 1996
rs ID: Unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies: In vitro expression in COS-7 cells. Less than 5% of residual ASM activity compared to wild-type ASM (Ida et al., 1996).
c.788T>A
p.L263X
Domain: phosphoesterase domain Type: Nonsense SIFT: MAF: NA
Composite Position: 11:6391853 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Takahashi et al., 1992
rs ID: rs120074120 Predicted effect: Probably pathogenic Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies: In vitro expression in COS-1 cells. Less than 5% of residual ASM activity compared to wild-type ASM (Takahashi et al., 1992).
c.796C>G
p.L266V
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.32) MAF: G=0.0002/1
Composite Position: 11:6391861 Found in NPA/B patients: No PolyPhen: benign:0.001
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs200681698 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.806C>T
p.A269V
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0.06) MAF: T=0.0002/1
Composite Position: 11:6391871 Found in NPA/B patients: No PolyPhen: benign:0.376
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs543834713 Predicted effect: Unknown significance Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.807C>T
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: T=0.0182/90
Composite Position: 11:6391872 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs35933246 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.808G>A
p.G270S
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.48) MAF: A=0.0002/1
Composite Position: 11:6391873 Found in NPA/B patients: No PolyPhen: probably-damaging:0.744
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs202244080 Predicted effect: Unknown significance Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.813T>C
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: C=0.0026/13
Composite Position: 11:6391878 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs61876771 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.839A>C
p.D280A
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6391904 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Pavl_-Pereira et al., 2005
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies: In vitro expression in ASM-deficient fibroblasts. Less than 5% of residual ASM activity compared to wild-type ASM (Pavl_-Pereira et al., 2005).
c.844C>A
p.P282T
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.1) MAF: A=0.0002/1
Composite Position: 11:6391909 Found in NPA/B patients: No PolyPhen: probably-damaging:0.994
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs199955808 Predicted effect: Unknown significance Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.847G>A
p.A283T
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.38) MAF: NA
Composite Position: 11:6391912 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Pittis et al., 2004
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies: In vitro expression in COS-1 cells. Less than 5% of residual ASM activity compared to wild-type ASM (Dardis et al., 2005).
c.842_849dupTCCCCGCA
p.H284Sfs*17
Domain: phosphoesterase domain Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6391914_6391921 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Zhang et al., 2013
rs ID: rs281860677 Predicted effect: Probably pathogenic Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.862C>G
p.H288D
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.3) MAF: G=0.0002/1
Composite Position: 11:6391927 Found in NPA/B patients: No PolyPhen: benign:0.001
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs529881058 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.869C>A
p.T290N
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0.01) MAF: NA
Composite Position: 11:6391934 Found in NPA/B patients: No PolyPhen: possibly-damaging:0.891
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs376259993 Predicted effect: Probably pathogenic Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.872G>A
p.R291H
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.06) MAF: A=0.0002/1
Composite Position: 11:6391937 Found in NPA/B patients: Yes PolyPhen: possibly-damaging:0.998
Exon/Intron: exon 2 Found in Controls: Yes Reference: Simonaro et al., 2002
rs ID: rs1803161 Predicted effect: Unknown significance Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.880C>A
p.Q294K
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0.01) MAF: NA
Composite Position: 11:6391945 Found in NPA/B patients: Yes PolyPhen: possibly-damaging:0.984
Exon/Intron: exon 2 Found in Controls: No Reference: Pavlu and Elleder 1997
rs ID: rs120074128 Predicted effect: Probably pathogenic Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies: In vitro expression in ASM-deficient fibroblasts. Less than 5% of residual ASM activity compared to wild-type ASM (Pavl_-Pereira et al., 2005).
c.886C>T
p.R296W
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0.01) MAF: NA
Composite Position: 11:6391951 Found in NPA/B patients: No PolyPhen: possibly-damaging:0.976
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs541061793 Predicted effect: Probably pathogenic Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.887G>A
p.R296Q
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.57) MAF: A=0.0166/83
Composite Position: 11:6391952 Found in NPA/B patients: Yes PolyPhen: benign:0.011
Exon/Intron: exon 2 Found in Controls: Yes Reference: Ricci et al., 2004
rs ID: rs35824453 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.890C>T
p.A297V
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (1) MAF: NA
Composite Position: 11:6391955 Found in NPA/B patients: No PolyPhen: benign:0.067
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs150815128 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.894G>C
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: NA
Composite Position: 11:6391959 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs371688255 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.897C>T
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: T=0.0002/1
Composite Position: 11:6391962 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs536760557 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.900C>T
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: NA
Composite Position: 11:6391965 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs368353322 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.901G>A
p.V301I
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.63) MAF: A=0.0032/16
Composite Position: 11:6391966 Found in NPA/B patients: No PolyPhen: benign:0.002
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs2723669 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.907G>A
p.A303T
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.53) MAF: A=0.0002/1
Composite Position: 11:6391972 Found in NPA/B patients: No PolyPhen: benign:0.004
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs570353618 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.909A>G
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: G=0.0006/3
Composite Position: 11:6391974 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs201134693 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.911T>C
p.L304P
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.13) MAF: NA
Composite Position: 11:6391976 Found in NPA/B patients: Yes PolyPhen: possibly-damaging:0.820
Exon/Intron: exon 2 Found in Controls: No Reference: Levran et al., 1992
rs ID: rs120074124 Predicted effect: Probably pathogenic Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies: In vitro expression in ASM-deficient fibroblasts. Less than 5% of residual ASM activity compared to wild-type ASM (Jones et al., 2008).
c.913G>A
p.V305M
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.88) MAF: A=0.0004/1
Composite Position: 11:6391978 Found in NPA/B patients: No PolyPhen: benign:0.340
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs199873765 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.937C>T
p.P313S
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0.01) MAF: NA
Composite Position: 11:6392002 Found in NPA/B patients: No PolyPhen: possibly-damaging:0.998
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs149991096 Predicted effect: Probably pathogenic Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.940G>A
p.V314M
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6392005 Found in NPA/B patients: Yes PolyPhen: possibly-damaging:0.998
Exon/Intron: exon 2 Found in Controls: No Reference: Desnick et al., 2010
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies: In vitro expression in 293-T cells. 21% of residual ASM activity compared to wild-type ASM (Desnick et al., 2010).
c.943T>C
p.Y315H
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6392008 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Ricci et al., 2004
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.945C>A
p.Y315X
Domain: phosphoesterase domain Type: Nonsense SIFT: MAF: NA
Composite Position: 11:6392010 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Rodriguez et al., 2009
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.953T>A
p.V318E
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6392018 Found in NPA/B patients: No PolyPhen: possibly-damaging:0.999
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs12575136 Predicted effect: Probably pathogenic Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.961C>T
p.H321Y
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6392026 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Sikora et al., 2003
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.968delG
p.S323Tfs*62
Domain: phosphoesterase domain Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6392033 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.971C>T
p.T324I
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.33) MAF: NA
Composite Position: 11:6392036 Found in NPA/B patients: No PolyPhen: benign:0.232
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs1050233 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.973_974insTGT
p.P325delinsLS
Domain: phosphoesterase domain Type: insertion SIFT: MAF: NA
Composite Position: 11:6392038 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs398123480 Predicted effect: Unknown significance Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.973C>G
p.P325A
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6392038 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies: In vitro expression in HeLa cells. Less than 5% of residual ASM activity compared to wild-type ASM (Rhein et al., 2013).
c.987C>T
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: T=0.0002/1
Composite Position: 11:6392052 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs572772760 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.991C>T
p.P331S
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0.04) MAF: NA
Composite Position: 11:6392056 Found in NPA/B patients: No PolyPhen: possibly-damaging:0.994
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs142476839 Predicted effect: Probably pathogenic Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.995C>T
p.P332L
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0.02) MAF: NA
Composite Position: 11:6392060 Found in NPA/B patients: No PolyPhen: possibly-damaging:0.999
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs202081954 Predicted effect: Probably pathogenic Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.995C>G
p.P332R
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0.03) MAF: NA
Composite Position: 11:6392060 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies:
c.996delC
p.F333Sfs*52
Domain: phosphoesterase domain Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6392061 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Levran et al., 1993
rs ID: rs387906289 Predicted effect: Probably pathogenic Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.1006G>A
p.G336S
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.67) MAF: NA
Composite Position: 11:6392071 Found in NPA/B patients: Yes PolyPhen: possibly-damaging:0.860
Exon/Intron: exon 2 Found in Controls: No Reference: Zhang et al., 2013
rs ID: rs281860667 Predicted effect: Unknown significance Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.1021C>T
p.R341C
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0.05) MAF: NA
Composite Position: 11:6392086 Found in NPA/B patients: No PolyPhen: possibly-damaging:0.715
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs369841281 Predicted effect: Probably pathogenic Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.1022G>A
p.R341H
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.19) MAF: NA
Composite Position: 11:6392087 Found in NPA/B patients: No PolyPhen: benign:0.000
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs200242334 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.1022G>C
p.R341P
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.23) MAF: NA
Composite Position: 11:6392087 Found in NPA/B patients: No PolyPhen: benign:0.096
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs200242334 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.1026G>T
p.W342C
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6392091 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Zhang et al., 2013
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.1028T>C
p.L343P
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0) MAF: NA
Composite Position: 11:6392093 Found in NPA/B patients: Yes PolyPhen: probably-damaging:1.0
Exon/Intron: exon 2 Found in Controls: No Reference: Pavlu and Elleder et al., 1997
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies: In vitro expression in ASM-deficient fibroblasts. Less than 5% of residual ASM activity compared to wild-type ASM (Pavlu-Pereira et al., 2005).
c.1033_1034insT
p.E345Vfs*46
Domain: phosphoesterase domain Type: Frameshift SIFT: MAF: NA
Composite Position: 11:6392098_6392099 Found in NPA/B patients: Yes PolyPhen:
Exon/Intron: exon 2 Found in Controls: No Reference: Manshadi et al., 2015
rs ID: unknown Predicted effect: Probably pathogenic Ref Link:
Curator note:
Functional studies:
c.1037C>T
p.A346V
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.5) MAF: NA
Composite Position: 11:6392102 Found in NPA/B patients: No PolyPhen: possibly-damaging:0.988
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs373508268 Predicted effect: Unknown significance Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.1044C>T
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: T=0.0006/3
Composite Position: 11:6392109 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs555187617 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.1054G>T
p.E352X
Domain: phosphoesterase domain Type: Nonsense SIFT: MAF: T=0.0002/1
Composite Position: 11:6392119 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs201550531 Predicted effect: Probably pathogenic Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note:
Functional studies:
c.1056G>T
p.E352D
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.45) MAF: NA
Composite Position: 11:6392121 Found in NPA/B patients: No PolyPhen: benign:0.356
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs144408432 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.1071C>T
p.(=)
Domain: phosphoesterase domain Type: Synonymous codon SIFT: MAF: T=0.0034/17
Composite Position: 11:6392136 Found in NPA/B patients: No PolyPhen:
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs72896268 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.1076C>A
p.A359D
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0.01) MAF: NA
Composite Position: 11:6392141 Found in NPA/B patients: Yes PolyPhen: possibly-damaging:0.929
Exon/Intron: exon 2 Found in Controls: No Reference: Simonaro et al., 2002
rs ID: unknown Predicted effect: Probably pathogenic Ref Link: https://grenada.lumc.nl/LOVD2/mendelian_genes
Curator note:
Functional studies: In vitro expression in COS-7 cells. Less than 5% of residual ASM activity compared to wild-type ASM (Acuna M., 2015).
c.1076C>T
p.A359V
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.56) MAF: NA
Composite Position: 11:6392141 Found in NPA/B patients: Yes PolyPhen: possibly-damaging:0.851
Exon/Intron: exon 2 Found in Controls: No Reference: Cho et al., 2009
rs ID: unknown Predicted effect: Unknown significance Ref Link:
Curator note:
Functional studies:
c.1081C>T
p.R361C
Domain: phosphoesterase domain Type: Missense SIFT: Damaging (0.03) MAF: NA
Composite Position: 11:6392146 Found in NPA/B patients: No PolyPhen: probably-damaging:0.958
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs370198638 Predicted effect: Probably pathogenic Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.1082G>A
p.R361H
Domain: phosphoesterase domain Type: Missense SIFT: Tolerated (0.64) MAF: NA
Composite Position: 11:6392147 Found in NPA/B patients: No PolyPhen: benign:0.000
Exon/Intron: exon 2 Found in Controls: Yes Reference:
rs ID: rs148892841 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note:
Functional studies:
c.1091+9C>T
NA
Domain: Type: Intronic variant SIFT: MAF: T=0.0008/3
Composite Position: 11:6392165 Found in NPA/B patients: No PolyPhen:
Exon/Intron: intron 2 Found in Controls: Yes Reference:
rs ID: rs143612450 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note: In silico analysis. No difference between WT and mutant sequence scores.
Functional studies:
c.1091+10G>A
NA
Domain: Type: Intronic variant SIFT: MAF: A=0.0004/1
Composite Position: 11:6392166 Found in NPA/B patients: No PolyPhen:
Exon/Intron: intron 2 Found in Controls: Yes Reference:
rs ID: rs148067213 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note: In silico analysis. No difference between WT and mutant sequence scores.
Functional studies:
c.1091+13C>T
NA
Domain: Type: Intronic variant SIFT: MAF: NA
Composite Position: 11:6392169 Found in NPA/B patients: No PolyPhen:
Exon/Intron: intron 2 Found in Controls: Yes Reference:
rs ID: rs371340833 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note: In silico analysis. No difference between WT and mutant sequence scores.
Functional studies:
c.1091+20A>T
NA
Domain: Type: Intronic variant SIFT: MAF: NA
Composite Position: 11:6392176 Found in NPA/B patients: No PolyPhen:
Exon/Intron: intron 2 Found in Controls: Yes Reference:
rs ID: rs373629757 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note: In silico analysis. No difference between WT and mutant sequence scores.
Functional studies:
c.1091+25G>C
NA
Domain: Type: Intronic variant SIFT: MAF: NA
Composite Position: 11:6392181 Found in NPA/B patients: No PolyPhen:
Exon/Intron: intron 2 Found in Controls: Yes Reference:
rs ID: rs375912494 Predicted effect: Probably benign Ref Link: http://evs.gs.washington.edu/EVS/
Curator note: In silico analysis. No difference between WT and mutant sequence scores.
Functional studies:
c.1091+30G>C
NA
</
Domain: Type: Intronic variant SIFT: MAF: NA
Composite Position: 11:6392186 Found in NPA/B patients: No PolyPhen:
Exon/Intron: intron 2 Found in Controls: Yes Reference:
rs ID: rs574634445 Predicted effect: Probably benign Ref Link: http://www.ncbi.nlm.nih.gov/snp
Curator note: In silico analysis. No difference between WT and mutant sequence scores.
Functional studies: