ClinVar Miner

Submissions for variant NM_080605.4(B3GALT6):c.35C>G (p.Ala12Gly) (rs900539403)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520086 SCV000619096 uncertain significance not provided 2018-02-09 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the B3GALT6 gene. The A12G variant has not been published as pathogenic or been reported as benign to our knowledge. The A12G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, this substitution occurs at a position that is not conserved across species and in silico analysis predicts this variant likely does not alter the protein structure/function. Nevertheless, data from control individuals was not available to assess whether A12G may be a common benign variant in the general population.
Invitae RCV000794417 SCV000933822 uncertain significance Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures; Ehlers-Danlos syndrome, progeroid type, 2 2018-07-09 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 12 of the B3GALT6 protein (p.Ala12Gly). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and glycine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with B3GALT6-related disease. ClinVar contains an entry for this variant (Variation ID: 450501). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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