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

dbSNP: rs748165078

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
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	ClinVar contains an entry for this variant (Variation ID: 553306). 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). 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 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.
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
Counsyl	RCV000668721	SCV000793368	likely pathogenic	Niemann-Pick disease, type A	2017-08-24	no assertion criteria provided	clinical testing	This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact [e-mail].