ClinVar Miner

Submissions for variant NM_032620.4(GTPBP3):c.964G>C (p.Ala322Pro)

gnomAD frequency: 0.00009  dbSNP: rs372174278
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000157593 SCV001367819 uncertain significance Combined oxidative phosphorylation defect type 23 2019-12-12 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3,PP5,BP6.
Labcorp Genetics (formerly Invitae), Labcorp RCV001850189 SCV002259739 uncertain significance not provided 2022-07-22 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 354 of the GTPBP3 protein (p.Ala354Pro). This variant is present in population databases (rs372174278, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of combined oxidative phosphorylation deficiency (PMID: 25434004). This variant is also known as p.Ala322Pro. ClinVar contains an entry for this variant (Variation ID: 180617). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects GTPBP3 function (PMID: 33619562). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001850189 SCV002526193 likely pathogenic not provided 2022-06-10 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect (reduction of GTPase activity and impaired tRNA modification) (Peng et al., 2021); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as A322P; This variant is associated with the following publications: (PMID: 26832457, 34426522, 33619562, 25434004)
OMIM RCV000157593 SCV000207372 pathogenic Combined oxidative phosphorylation defect type 23 2014-12-04 no assertion criteria provided literature only

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