ClinVar Miner

Submissions for variant NM_152743.4(BRAT1):c.491C>T (p.Ala164Val) (rs771600489)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523294 SCV000619965 uncertain significance not provided 2018-06-26 criteria provided, single submitter clinical testing The A164V variant in the BRAT1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A164V variant is observed in 5/123318 (0.004%) alleles from individuals of non-Finnish European background, in large population cohorts (Lek et al., 2016). The A164V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret A164V as a variant of uncertain significance.
Invitae RCV000650120 SCV000771957 uncertain significance Rigidity and multifocal seizure syndrome, lethal neonatal 2018-01-08 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 164 of the BRAT1 protein (p.Ala164Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs771600489, ExAC 0.003%). This variant has not been reported in the literature in individuals with BRAT1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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