ClinVar Miner

Submissions for variant NM_033109.5(PNPT1):c.1382T>C (p.Val461Ala)

gnomAD frequency: 0.00003  dbSNP: rs752666494
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001558639 SCV001780632 uncertain significance not provided 2023-04-21 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001558639 SCV002292638 likely pathogenic not provided 2023-12-31 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 461 of the PNPT1 protein (p.Val461Ala). This variant is present in population databases (rs752666494, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of combined oxidative phosphorylation deficiency (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1195522). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PNPT1 protein function with a negative predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Revvity Omics, Revvity RCV001558639 SCV003809126 uncertain significance not provided 2021-02-04 criteria provided, single submitter clinical testing

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