ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.1343A>G (p.Tyr448Cys)

gnomAD frequency: 0.00001  dbSNP: rs747143343
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001004367 SCV001163309 likely pathogenic Niemann-Pick disease, type A 2024-03-05 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001384265 SCV001583694 pathogenic Niemann-Pick disease, type B; Niemann-Pick disease, type A 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 448 of the SMPD1 protein (p.Tyr448Cys). This variant is present in population databases (rs747143343, gnomAD 0.01%). This missense change has been observed in individual(s) with Niemann-Pick disease type A or B (PMID: 8693491, 29485843, 31122880). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as Y446C. ClinVar contains an entry for this variant (Variation ID: 242451). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects SMPD1 function (PMID: 8693491). For these reasons, this variant has been classified as Pathogenic.
Natera, Inc. RCV001004367 SCV002092271 pathogenic Niemann-Pick disease, type A 2017-03-17 no assertion criteria provided clinical testing

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