ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.1033G>A (p.Ala345Thr) (rs150934009)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000619849 SCV000739601 likely benign Cardiovascular phenotype 2016-12-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Subpopulation frequency in support of benign classification
GeneDx RCV000200606 SCV000250649 likely benign not specified 2018-01-04 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000474882 SCV000550374 uncertain significance Shprintzen-Goldberg syndrome 2018-12-07 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 345 of the SKI protein (p.Ala345Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs150934009, ExAC 0.05%) but has not been reported in the literature in individuals with a SKI-related disease. ClinVar contains an entry for this variant (Variation ID: 213666). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The threonine amino acid residue is also found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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