ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.1071C>T (p.Ala357=) (rs72896268)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000079188 SCV000111057 benign not specified 2013-08-22 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000079188 SCV000305088 likely benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000394529 SCV000372937 likely benign Niemann-Pick disease, type A 2018-01-12 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae RCV001082924 SCV000755907 benign Niemann-Pick disease, type B; Niemann-Pick disease, type A 2020-12-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000079188 SCV001442606 benign not specified 2020-10-05 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000675396 SCV001502022 likely benign not provided 2020-11-01 criteria provided, single submitter clinical testing
Nilou-Genome Lab RCV000394529 SCV001716378 benign Niemann-Pick disease, type A 2021-05-18 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000675396 SCV000801066 benign not provided 2015-10-22 no assertion criteria provided clinical testing
Broad Institute Rare Disease Group, Broad Institute RCV001249054 SCV001423000 likely benign Sphingomyelin/cholesterol lipidosis 2020-01-22 no assertion criteria provided curation The c.1071C>T (p.Ala357=) variant in SMPD1 (also known as p.Ala355= due to a difference in cDNA numbering) has not been previously reported in individuals with Niemann-Pick disease, but has been identified in 1.062% (110/10360) of Ashkenazi Jewish chromosomes, 0.807% (1037/128468) of European (non-Finnish) chromosomes, including 9 homozygotes, and 0.378% (134/35428) of Latino chromosomes. This variant has also been reported in ClinVar (VariationID: 93310) as a VUS by Illumina Clinical Services Laboratory, as likely benign by PreventionGenetics, and as benign by Invitae, EGL Genetic Diagnostics, and Mayo Clinic Genetic Testing Laboratories. 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, BP4, BP7 (Richards 2015).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.