Submissions for variant NM_000543.5(SMPD1):c.107_136dup (p.Leu45_Ala46insValLeuAlaLeuAlaLeuAlaLeuAlaLeu)

dbSNP: rs1554933798

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002904117	SCV003253788	uncertain significance	Niemann-Pick disease, type B; Niemann-Pick disease, type A	2022-04-18	criteria provided, single submitter	clinical testing	This variant, c.107_136dup, results in the insertion of 10 amino acid(s) of the SMPD1 protein (p.Val36_Leu45dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with SMPD1-related conditions. 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV003481347	SCV004225359	uncertain significance	not provided	2023-04-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004744472	SCV005348756	uncertain significance	SMPD1-related disorder	2024-04-17	no assertion criteria provided	clinical testing	The SMPD1 c.107_136dup30 variant is predicted to result in an in-frame duplication (p.Val36_Leu45dup). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.13% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.