Submissions for variant NM_000543.5(SMPD1):c.108GCTGGC[7] (p.38AL[7])

dbSNP: rs3838786

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001247390	SCV001420807	uncertain significance	Niemann-Pick disease, type B; Niemann-Pick disease, type A	2022-09-27	criteria provided, single submitter	clinical testing	This variant, c.138_143dup, results in the insertion of 2 amino acid(s) of the SMPD1 protein (p.Ala48_Leu49dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMPD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 971581). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV001567445	SCV001791128	likely benign	not provided	2021-05-27	criteria provided, single submitter	clinical testing	In-frame insertion of 2 amino acids in a repetitive region with no known function; Has not been previously published as pathogenic or benign to our knowledge
Mayo Clinic Laboratories, Mayo Clinic	RCV001567445	SCV002541118	uncertain significance	not provided	2021-11-09	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003945945	SCV004767664	likely benign	SMPD1-related disorder	2019-10-24	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).