Submissions for variant NM_005859.5(PURA):c.487C>T (p.Gln163Ter)

dbSNP: rs1554129091

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000523168	SCV000620655	pathogenic	not provided	2017-09-15	criteria provided, single submitter	clinical testing	The Q163X variant in the PURA gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause a premature stop codon, resulting in protein truncation of the last 160 amnio acids. The Q163X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret Q163X as a pathogenic variant
Invitae	RCV000652454	SCV000774324	pathogenic	PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome	2022-11-15	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PURA protein in which other variant(s) (p.Tyr261*, p.Gln186*) have been determined to be pathogenic (PMID: 25439098). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 451895). This variant has not been reported in the literature in individuals affected with PURA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln163*) in the PURA gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 160 amino acid(s) of the PURA protein.
3billion	RCV000652454	SCV004013559	pathogenic	PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome		criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. The variant is predicted to result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region. The variant has been previously reported as de novo in a similarly affected individual (PMID: 35118825). The variant has been reported at least twice as pathogenic without evidence for the classification (ClinVar ID: VCV000451895 / PMID: 33726816). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.