ClinVar Miner

Submissions for variant NM_033109.5(PNPT1):c.574C>T (p.Arg192Ter)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3billion, Medical Genetics RCV002283958 SCV002573219 pathogenic Autosomal recessive nonsyndromic hearing loss 70 2022-09-01 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Stop-gained (nonsense) is 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. Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID: 28594066). The variant has been reported to be associated with PNPT1-related disorder (PMID: 28594066). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
GeneDx RCV003225227 SCV003921725 pathogenic not provided 2023-04-27 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32020600, 27535533, 28594066)
Labcorp Genetics (formerly Invitae), Labcorp RCV003225227 SCV005812722 pathogenic not provided 2024-11-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg192*) in the PNPT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PNPT1 are known to be pathogenic (PMID: 28594066, 30244537). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with PNPT1-related conditions (PMID: 28594066, 32020600). ClinVar contains an entry for this variant (Variation ID: 1705644). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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