ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.11C>T (p.Ala4Val) (rs1085307767)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000490080 SCV000577262 uncertain significance not provided 2017-04-06 criteria provided, single submitter clinical testing The A4V variant of uncertain significance in the SKI gene has not been published as pathogenic or been reported as benign to our knowledge. Data from control individuals was not available to assess whether A4V may be a common benign variant in the general population. However, the A4V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Furthermore, 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.
Invitae RCV000703987 SCV000832919 uncertain significance Shprintzen-Goldberg syndrome 2018-05-15 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 4 of the SKI protein (p.Ala4Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. 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 SKI-related disease. ClinVar contains an entry for this variant (Variation ID: 426734). 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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