ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.1253G>A (p.Arg418Gln)

gnomAD frequency: 0.00008  dbSNP: rs767722360
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002108100 SCV002393893 likely benign Niemann-Pick disease, type B; Niemann-Pick disease, type A 2024-03-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002222756 SCV002500349 uncertain significance not specified 2022-03-13 criteria provided, single submitter clinical testing Variant summary: SMPD1 c.1253G>A (p.Arg418Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 248074 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in SMPD1 causing Niemann-Pick Disease (6e-05 vs 0.0022), allowing no conclusion about variant significance. c.1253G>A has been reported in the literature as a non-informative genotype (second allele not reported/specified) among cohorts of patients with Parkinson Disease (example, Robak_2017, Alcalay_2019). These report(s) do not provide unequivocal conclusions about association of the variant with Niemann-Pick Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Revvity Omics, Revvity RCV003138079 SCV003822015 uncertain significance not provided 2021-02-18 criteria provided, single submitter clinical testing

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