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
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