rs1264586139
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003036.4(SKI):c.2168C>A(p.Ala723Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000262 in 1,525,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A723P) has been classified as Uncertain significance.
Frequency
Consequence
NM_003036.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SKI | NM_003036.4 | c.2168C>A | p.Ala723Asp | missense_variant | 7/7 | ENST00000378536.5 | NP_003027.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SKI | ENST00000378536.5 | c.2168C>A | p.Ala723Asp | missense_variant | 7/7 | 1 | NM_003036.4 | ENSP00000367797.4 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000830 AC: 1AN: 120486Hom.: 0 AF XY: 0.0000151 AC XY: 1AN XY: 66340
GnomAD4 exome AF: 0.00000218 AC: 3AN: 1373126Hom.: 0 Cov.: 32 AF XY: 0.00000295 AC XY: 2AN XY: 677058
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152060Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74274
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2016 | The p.A723D variant (also known as c.2168C>A), located in coding exon 7 of the SKI gene, results from a C to A substitution at nucleotide position 2168. The alanine at codon 723 is replaced by aspartic acid, an amino acid with dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 3637 samples (7274 alleles) with coverage at this position. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
Shprintzen-Goldberg syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 11, 2022 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 520155). This variant has not been reported in the literature in individuals affected with SKI-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 723 of the SKI protein (p.Ala723Asp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at