chr1-2228908-A-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_003036.4(SKI):āc.142A>Cā(p.Lys48Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000142 in 1,411,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. K48K) has been classified as Likely benign.
Frequency
Consequence
NM_003036.4 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 | UniProt |
---|---|---|---|---|---|---|---|
SKI | NM_003036.4 | c.142A>C | p.Lys48Gln | missense_variant | 1/7 | ENST00000378536.5 | |
SKI | XM_005244775.4 | c.142A>C | p.Lys48Gln | missense_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SKI | ENST00000378536.5 | c.142A>C | p.Lys48Gln | missense_variant | 1/7 | 1 | NM_003036.4 | P1 | |
SKI | ENST00000704337.1 | n.137+1384A>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000334 AC: 5AN: 149590Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000116 AC: 1AN: 86544Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 49800
GnomAD4 exome AF: 0.0000119 AC: 15AN: 1261598Hom.: 0 Cov.: 31 AF XY: 0.00000803 AC XY: 5AN XY: 623042
GnomAD4 genome AF: 0.0000334 AC: 5AN: 149590Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 72942
ClinVar
Submissions by phenotype
Shprintzen-Goldberg syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 19, 2023 | 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: 432531). 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 0.003%). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 48 of the SKI protein (p.Lys48Gln). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 18, 2024 | The p.K48Q variant (also known as c.142A>C), located in coding exon 1 of the SKI gene, results from an A to C substitution at nucleotide position 142. The lysine at codon 48 is replaced by glutamine, an amino acid with similar properties. This amino acid position is conserved. 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 alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 13, 2023 | 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 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at