Submissions for variant NM_000543.5(SMPD1):c.813T>C (p.Pro271=)

gnomAD frequency: 0.00500  dbSNP: rs61876771

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000306517	SCV000330990	benign	not specified	2015-08-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000287994	SCV000372932	likely benign	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 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	RCV000960163	SCV001107116	benign	Niemann-Pick disease, type B; Niemann-Pick disease, type A	2024-01-31	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001249057	SCV001423004	likely benign	Sphingomyelin/cholesterol lipidosis	2020-01-22	criteria provided, single submitter	curation	The c.813T>C (p.Pro271=) variant in SMPD1 (also known as p.Pro269= due to a difference in cDNA numbering) has not been previously reported in individuals with Niemann-Pick disease but has been identified in 0.793% (1020/128622) of European (non-Finnish) chromosomes and 0.759% (190/25022) of European (Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs61876771). 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).
GeneDx	RCV001675769	SCV001893003	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001675769	SCV001961265	likely benign	not provided	2023-07-01	criteria provided, single submitter	clinical testing	SMPD1: BP4, BP7
Ambry Genetics	RCV002418105	SCV002681744	likely benign	Inborn genetic diseases	2022-03-25	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000306517	SCV001929575	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001675769	SCV001972126	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000287994	SCV002091699	benign	Niemann-Pick disease, type A	2017-06-30	no assertion criteria provided	clinical testing