ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.1718G>C (p.Trp573Ser)

dbSNP: rs2134024060
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3billion RCV002052044 SCV002318447 uncertain significance Niemann-Pick disease, type A 2022-03-22 criteria provided, single submitter clinical testing Same or different nucleotide change resulting in same amino acid change has been previously reported to be associated with SMPD1 related disorder (PMID:32292456). It is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.874>=0.6, 3CNET: 0.972>=0.75). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.
Invitae RCV002550507 SCV002954024 uncertain significance Niemann-Pick disease, type B; Niemann-Pick disease, type A 2022-02-08 criteria provided, single submitter clinical testing This sequence change replaces tryptophan, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 573 of the SMPD1 protein (p.Trp573Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Niemann-Pick disease (PMID: 32292456). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SMPD1 protein function. 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.
Genetics Laboratory, University of Sistan and Baluchestan RCV002052044 SCV002556344 likely pathogenic Niemann-Pick disease, type A no assertion criteria provided clinical testing

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