ClinVar Miner

Submissions for variant NM_020631.6(PLEKHG5):c.100G>A (p.Ala34Thr)

gnomAD frequency: 0.00004  dbSNP: rs760113279
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001313288 SCV001503778 uncertain significance Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C 2022-10-25 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 34 of the PLEKHG5 protein (p.Ala34Thr). This variant is present in population databases (rs760113279, gnomAD 0.1%). This missense change has been observed in individual(s) with familial amyotrophic lateral sclerosis (PMID: 28160950). This variant is also known as c.307G>A (p.A103T). ClinVar contains an entry for this variant (Variation ID: 1014541). 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 RCV002438700 SCV002751121 uncertain significance Inborn genetic diseases 2022-05-23 criteria provided, single submitter clinical testing The p.A34T variant (also known as c.100G>A), located in coding exon 2 of the PLEKHG5 gene, results from a G to A substitution at nucleotide position 100. The alanine at codon 34 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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.

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