ClinVar Miner

Submissions for variant NM_007254.4(PNKP):c.1315C>T (p.Arg439Ter) (rs539286945)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000434738 SCV000517263 pathogenic not provided 2015-05-19 criteria provided, single submitter clinical testing The R439X nonsense variant in the PNKP gene is predicted to cause loss of normal protein function eitherthrough protein truncation or nonsense-mediated mRNA decay. It was not observed in approximately 6,000individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, but the 1000Genomes Project reports R439X was observed in 1/198 (0.5%) alleles from individuals of Nigerianbackground. Although the R439X variant has not been reported previously to our knowledge, it is expected to be a pathogenic variant.
Invitae RCV000821367 SCV000962122 pathogenic Early infantile epileptic encephalopathy 12 2018-08-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg439*) in the PNKP gene. It is expected to result in an absent or disrupted protein product. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with PNKP-related disease. ClinVar contains an entry for this variant (Variation ID: 379820). Loss-of-function variants in PNKP are known to be pathogenic (PMID: 20118933, 25728773). For these reasons, this variant has been classified as Pathogenic.

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