ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.305A>G (p.Asn102Ser)

gnomAD frequency: 0.00001  dbSNP: rs373475928
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001069771 SCV001234964 uncertain significance Niemann-Pick disease, type B; Niemann-Pick disease, type A 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 102 of the SMPD1 protein (p.Asn102Ser). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs373475928, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with SMPD1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003235464 SCV003934637 uncertain significance not specified 2023-05-05 criteria provided, single submitter clinical testing Variant summary: SMPD1 c.305A>G (p.Asn102Ser) results in a conservative amino acid change located in the Saposin B type domain (IPR008139) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 250196 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.305A>G in individuals affected with Niemann-Pick Disease and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc. RCV001836112 SCV002091671 uncertain significance Niemann-Pick disease, type A 2017-05-05 no assertion criteria provided clinical testing

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