rs557289756
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The ENST00000378536.5(SKI):c.1205G>A(p.Arg402Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,611,980 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R402G) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000378536.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SKI | NM_003036.4 | c.1205G>A | p.Arg402Gln | missense_variant | 3/7 | ENST00000378536.5 | NP_003027.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SKI | ENST00000378536.5 | c.1205G>A | p.Arg402Gln | missense_variant | 3/7 | 1 | NM_003036.4 | ENSP00000367797 | P1 | |
SKI | ENST00000704337.1 | n.373G>A | non_coding_transcript_exon_variant | 3/4 | ||||||
SKI | ENST00000478223.2 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152126Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250350Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135482
GnomAD4 exome AF: 0.0000158 AC: 23AN: 1459736Hom.: 1 Cov.: 32 AF XY: 0.0000207 AC XY: 15AN XY: 726260
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74444
ClinVar
Submissions by phenotype
Shprintzen-Goldberg syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 27, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 04, 2024 | - - |
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 12, 2024 | The p.R402Q variant (also known as c.1205G>A), located in coding exon 3 of the SKI gene, results from a G to A substitution at nucleotide position 1205. The arginine at codon 402 is replaced by glutamine, an amino acid with highly 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at