ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.820A>G (p.Met274Val)

gnomAD frequency: 0.00001  dbSNP: rs763437061
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001890099 SCV002142918 uncertain significance Niemann-Pick disease, type B; Niemann-Pick disease, type A 2021-11-21 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 274 of the SMPD1 protein (p.Met274Val). This variant is present in population databases (rs763437061, gnomAD 0.005%). 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. 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.
Ambry Genetics RCV002425165 SCV002681234 uncertain significance Inborn genetic diseases 2022-09-24 criteria provided, single submitter clinical testing The p.M274V variant (also known as c.820A>G), located in coding exon 2 of the SMPD1 gene, results from an A to G substitution at nucleotide position 820. The methionine at codon 274 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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