ClinVar Miner

Submissions for variant NM_198253.3(TERT):c.3172G>T (p.Ala1058Ser)

gnomAD frequency: 0.00001  dbSNP: rs1478959357
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003103839 SCV000942149 uncertain significance Dyskeratosis congenita, autosomal dominant 2; Idiopathic Pulmonary Fibrosis 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 1058 of the TERT protein (p.Ala1058Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with TERT-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV004559672 SCV002609719 uncertain significance Dyskeratosis congenita 2022-06-08 criteria provided, single submitter clinical testing The p.A1058S variant (also known as c.3172G>T), located in coding exon 15 of the TERT gene, results from a G to T substitution at nucleotide position 3172. The alanine at codon 1058 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. 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.
GeneDx RCV003238814 SCV003936750 uncertain significance not provided 2023-01-02 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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