Submissions for variant NM_003036.4(SKI):c.1735G>A (p.Ala579Thr)

gnomAD frequency: 0.00002  dbSNP: rs370558210

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768314	SCV000898974	uncertain significance	Shprintzen-Goldberg syndrome	2021-03-30	criteria provided, single submitter	clinical testing	SKI NM_003036.3 exon 5 p.Ala579Thr (c.1735G>A): This variant has not been reported in the literature and is present in 0.01% (3/27314) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/1-2235992-G-A). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000768314	SCV001205754	likely benign	Shprintzen-Goldberg syndrome	2025-02-02	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000768314	SCV001367319	uncertain significance	Shprintzen-Goldberg syndrome	2020-01-20	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: BP4.
GeneDx	RCV001563560	SCV001786530	uncertain significance	not provided	2024-02-27	criteria provided, single submitter	clinical testing	Reported in an individual with Hodgkin lymphoma and an SKI-related phenotype (Bravo Gomez et al., (2021) https://www.degruyter.com/document/doi/10.1515/cclm-2021-5020/html); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: BravoGomez2021[abstract])
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV000768314	SCV002768739	uncertain significance	Shprintzen-Goldberg syndrome	2020-05-25	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3B-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0107 - This gene is known to be associated with autosomal dominant disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from an alanine to a threonine (exon 5). (N) 0251 - Variant is heterozygous. (N) 0302 - Variant is present in gnomAD <0.001 for a dominant condition (9 heterozygotes, 0 homozygotes). (P) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (2 heterozygotes, 0 homozygotes). (N) 0502 - Missense variant with conflicting in silico predictions and/or uninformative conservation. (N) 0600 - Variant is located in an annotated domain or motif (coiled-coil region; PDB). (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0804 - Variant has previously been described as variant of uncertain significance in multiple independent cases (ClinVar, LOVD). (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign
Ambry Genetics	RCV004027214	SCV005020205	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-01-16	criteria provided, single submitter	clinical testing	The p.A579T variant (also known as c.1735G>A), located in coding exon 5 of the SKI gene, results from a G to A substitution at nucleotide position 1735. The alanine at codon 579 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001563560	SCV001932362	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001563560	SCV001965910	uncertain significance	not provided		no assertion criteria provided	clinical testing