Submissions for variant NM_000543.5(SMPD1):c.349G>A (p.Val117Met)

gnomAD frequency: 0.00011  dbSNP: rs202206564

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000297445	SCV000372924	uncertain significance	Niemann-Pick disease, type A	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Eurofins Ntd Llc (ga)	RCV000728558	SCV000856149	uncertain significance	not provided	2017-08-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001085400	SCV001073248	benign	Niemann-Pick disease, type B; Niemann-Pick disease, type A	2024-03-04	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000728558	SCV005412280	uncertain significance	not provided	2023-10-17	criteria provided, single submitter	clinical testing	BP4
Natera, Inc.	RCV000297445	SCV002091675	likely benign	Niemann-Pick disease, type A	2018-06-12	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003950024	SCV004773439	likely benign	SMPD1-related disorder	2023-02-08	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).