ClinVar Miner

Submissions for variant NM_007254.4(PNKP):c.422G>A (p.Arg141Gln)

gnomAD frequency: 0.00001  dbSNP: rs570013652
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188428 SCV000242041 uncertain significance not provided 2016-07-06 criteria provided, single submitter clinical testing The R141Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations, and it was not observed with any significant frequency in the 1000 Genomes Project. The R141Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000576288 SCV000677064 likely benign Developmental and epileptic encephalopathy, 12 2023-09-22 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000188428 SCV002543962 likely benign not provided 2022-04-01 criteria provided, single submitter clinical testing PNKP: BP4
Ambry Genetics RCV002327014 SCV002629659 uncertain significance Inborn genetic diseases 2018-08-09 criteria provided, single submitter clinical testing The p.R141Q variant (also known as c.422G>A), located in coding exon 3 of the PNKP gene, results from a G to A substitution at nucleotide position 422. The arginine at codon 141 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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