Submissions for variant NM_000543.5(SMPD1):c.362T>C (p.Leu121Pro)

dbSNP: rs1554934109

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000671945	SCV000796989	uncertain significance	Niemann-Pick disease, type A	2018-01-08	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000671945	SCV004205509	likely pathogenic	Niemann-Pick disease, type A	2023-04-25	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV005240439	SCV005884231	likely pathogenic	Sphingomyelin/cholesterol lipidosis	2024-12-10	criteria provided, single submitter	clinical testing	Variant summary: SMPD1 c.362T>C (p.Leu121Pro) results in a non-conservative amino acid change located in the saposin B type domain (IPR008139) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251300 control chromosomes (gnomAD). c.362T>C has been reported in the literature in individuals including homozygotes affected with Niemann-Pick Disease (examples: Reunert_2015; Velez-Pinos_2023). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 26981555, 36779112). ClinVar contains an entry for this variant (Variation ID: 556008). Based on the evidence outlined above, the variant was classified as likely pathogenic.