ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.441G>A (p.Val147=)

gnomAD frequency: 0.00241  dbSNP: rs148944108
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000325277 SCV000340675 benign not specified 2016-03-18 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000357086 SCV000372925 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001081186 SCV001118310 benign Niemann-Pick disease, type B; Niemann-Pick disease, type A 2024-01-31 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000970717 SCV001148165 uncertain significance not provided 2016-08-01 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001248936 SCV001422714 uncertain significance Sphingomyelin/cholesterol lipidosis 2020-01-22 criteria provided, single submitter curation The c.441G>A (p.Val147=) variant in SMPD1 (also known as p.Val145= due to a difference in cDNA numbering) has not been previously reported in individuals with Niemann-Pick disease but has been identified in 0.585% (146/24956) of African chromosomes, 0.133% (47/35414) of Latino chromosomes, and 0.0147% (19/129008) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs148944108). This variant has been reported in ClinVar as a VUS by Illumina and Benign by EGL Genetic Diagnostics (Variation ID: 287033). Computational tools do suggest an impact to splicing with the strong activation of a cryptic donor site. However, this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the c.441G>A variant is uncertain. ACMG/AMP Criteria applied: BS1 (Richards 2015).
Natera, Inc. RCV000357086 SCV002091677 likely benign Niemann-Pick disease, type A 2017-05-05 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV003957470 SCV004771488 likely benign SMPD1-related disorder 2019-08-20 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).

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