ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.1091+9C>T

gnomAD frequency: 0.00103  dbSNP: rs143612450
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000372496 SCV000338426 likely benign not specified 2016-01-21 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000294629 SCV000372938 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.
Invitae RCV000889391 SCV001033069 benign Niemann-Pick disease, type B; Niemann-Pick disease, type A 2024-01-29 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001249053 SCV001422999 likely benign Sphingomyelin/cholesterol lipidosis 2020-01-22 criteria provided, single submitter curation The c.1091+9C>T variant in SMPD1 has not been previously reported in individuals with Niemann-Pick disease, but has been identified in 0.317% (79/24926) of African chromosomes, 0.008% (3/35418) of Latino chromosomes, and 0.001% (1/127714) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD,; dbSNP rs143612450). This variant has also been reported in ClinVar (VariationID: 285417) as a VUS by Illumina Clinical services Laboratory and as likely benign by EGL Genetic Diagnostics. Computational prediction tools, including splice predictors, and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely benign. ACMG/AMP Criteria applied: BS1, BP7, BP4 (Richards 2015).
Natera, Inc. RCV000294629 SCV002092262 likely benign Niemann-Pick disease, type A 2017-05-05 no assertion criteria provided clinical testing

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