ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.464C>G (p.Ala155Gly) (rs559020511)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000461900 SCV000896266 uncertain significance Shprintzen-Goldberg syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000413541 SCV000492202 uncertain significance not specified 2016-11-29 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SKI gene. The A155G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, the A155G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Nonetheless, this substitution occurs at a position that is conserved across species, and two of three in silico programs predict this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. This result cannot be interpreted for diagnosis or used for family member screening at this time.
Invitae RCV000461900 SCV000550384 uncertain significance Shprintzen-Goldberg syndrome 2017-04-24 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 155 of the SKI protein (p.Ala155Gly). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and glycine. This variant is present in population databases (rs559020511, ExAC 0.01%) but has not been reported in the literature in individuals with a SKI-related disease. ClinVar contains an entry for this variant (Variation ID: 373594). 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but 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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