ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.581dup (p.Ala195fs)

dbSNP: rs748165078
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668721 SCV000793368 likely pathogenic Niemann-Pick disease, type A 2017-08-24 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001310952 SCV001500950 pathogenic not provided 2020-10-01 criteria provided, single submitter clinical testing
3billion RCV000668721 SCV002059000 pathogenic Niemann-Pick disease, type A 2022-01-03 criteria provided, single submitter clinical testing Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000553306, PMID:15241805).It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000016, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Baylor Genetics RCV000668721 SCV004205519 pathogenic Niemann-Pick disease, type A 2024-03-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003767966 SCV004569718 pathogenic Niemann-Pick disease, type B; Niemann-Pick disease, type A 2023-04-26 criteria provided, single submitter clinical testing This premature translational stop signal has been observed in individual(s) with Niemann-Pick disease (PMID: 33675270). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 553306). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Ala195Serfs*14) in the SMPD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMPD1 are known to be pathogenic (PMID: 12369017, 15221801).
Rare Genetic Disease Lab, Dept of Zoology, Government Postgraduate College Dargai Malakand, Higher Education Govt. of Khyber Pakhtunkhwa RCV000668721 SCV005038953 pathogenic Niemann-Pick disease, type A 2024-03-04 criteria provided, single submitter research

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