ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.2056G>A (p.Ala686Thr)

gnomAD frequency: 0.00006  dbSNP: rs756553942
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000195941 SCV000250695 uncertain significance not provided 2022-01-04 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain clinical significance (ClinVar Variant ID#213709); This variant is associated with the following publications: (PMID: 26582918)
Invitae RCV001302172 SCV001491366 uncertain significance Shprintzen-Goldberg syndrome 2023-11-18 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 686 of the SKI protein (p.Ala686Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SKI-related conditions. ClinVar contains an entry for this variant (Variation ID: 213709). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SKI protein function with a negative predictive value of 95%. 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 RCV002415842 SCV002727583 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-03-01 criteria provided, single submitter clinical testing The p.A686T variant (also known as c.2056G>A), located in coding exon 7 of the SKI gene, results from a G to A substitution at nucleotide position 2056. The alanine at codon 686 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV001302172 SCV002790949 uncertain significance Shprintzen-Goldberg syndrome 2022-04-06 criteria provided, single submitter clinical testing

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