Submissions for variant NM_000543.5(SMPD1):c.8G>A (p.Arg3His)

gnomAD frequency: 0.00063  dbSNP: rs199836262

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000397745	SCV000332919	uncertain significance	not provided	2017-12-21	criteria provided, single submitter	clinical testing
Counsyl	RCV000674958	SCV000800374	uncertain significance	Niemann-Pick disease, type A	2018-06-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000819250	SCV000959900	likely benign	Niemann-Pick disease, type B; Niemann-Pick disease, type A	2024-12-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000674958	SCV001264241	uncertain significance	Niemann-Pick disease, type A	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Baylor Genetics	RCV000674958	SCV001520790	uncertain significance	Niemann-Pick disease, type A	2020-08-27	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx	RCV000397745	SCV002762253	uncertain significance	not provided	2022-12-12	criteria provided, single submitter	clinical testing	Identified in the heterozygous state in a patient with intellectual disability, short stature, microcephaly, and dysmorphic features who has other variants that may explain the phenotype (Qiao et al., 2017); Identified in the heterozygous state in a patient with a suspected lysosomal storage disease; however, a second variant was not reported (Fernandez-Marmiesse et al., 2014); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24767253, 28475290)
PreventionGenetics, part of Exact Sciences	RCV003417882	SCV004116522	uncertain significance	SMPD1-related disorder	2023-08-17	criteria provided, single submitter	clinical testing	The SMPD1 c.8G>A variant is predicted to result in the amino acid substitution p.Arg3His. This variant has been reported in the heterozygous state in an individual with a lysosomal storage disorder, however no additional evidence was provided to support the pathogenicity of this variant (see Table 5 in Fernández-Marmiesse et al. 2014. PubMed ID: 24767253). This variant is reported in 0.11% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-6411836-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc.	RCV001276409	SCV001462672	uncertain significance	Sphingomyelin/cholesterol lipidosis	2017-05-05	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000397745	SCV001744240	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000397745	SCV001973176	likely benign	not provided		no assertion criteria provided	clinical testing