ClinVar Miner

Submissions for variant NM_007055.4(POLR3A):c.4057A>G (p.Met1353Val)

gnomAD frequency: 0.00051  dbSNP: rs147168447
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000596117 SCV000707578 uncertain significance not provided 2017-04-03 criteria provided, single submitter clinical testing
GeneDx RCV000596117 SCV001820766 uncertain significance not provided 2019-07-12 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV000596117 SCV002119060 uncertain significance not provided 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1353 of the POLR3A protein (p.Met1353Val). This variant is present in population databases (rs147168447, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with POLR3A-related conditions. ClinVar contains an entry for this variant (Variation ID: 501275). 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 POLR3A protein function. 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.
Ambry Genetics RCV002532574 SCV003736340 uncertain significance Inborn genetic diseases 2022-01-10 criteria provided, single submitter clinical testing The c.4057A>G (p.M1353V) alteration is located in exon 31 (coding exon 31) of the POLR3A gene. This alteration results from a A to G substitution at nucleotide position 4057, causing the methionine (M) at amino acid position 1353 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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