ClinVar Miner

Submissions for variant NM_001130823.3(DNMT1):c.3157G>A (p.Ala1053Thr)

gnomAD frequency: 0.00004  dbSNP: rs370786558
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001653092 SCV001871254 uncertain significance not provided 2022-02-08 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
Fulgent Genetics, Fulgent Genetics RCV002488445 SCV002785919 uncertain significance Autosomal dominant cerebellar ataxia, deafness and narcolepsy; Hereditary sensory neuropathy-deafness-dementia syndrome 2021-10-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002538540 SCV003277492 uncertain significance Hereditary sensory neuropathy-deafness-dementia syndrome 2023-07-13 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1053 of the DNMT1 protein (p.Ala1053Thr). This variant is present in population databases (rs370786558, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with DNMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1254310). 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 DNMT1 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.

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