rs764317955
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_003036.4(SKI):c.1271C>T(p.Pro424Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,612,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P424P) has been classified as Likely benign.
Frequency
Consequence
NM_003036.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SKI | NM_003036.4 | c.1271C>T | p.Pro424Leu | missense_variant | 4/7 | ENST00000378536.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SKI | ENST00000378536.5 | c.1271C>T | p.Pro424Leu | missense_variant | 4/7 | 1 | NM_003036.4 | P1 | |
SKI | ENST00000507179.1 | n.254C>T | non_coding_transcript_exon_variant | 1/2 | 2 | ||||
SKI | ENST00000704337.1 | n.439C>T | non_coding_transcript_exon_variant | 4/4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000165 AC: 4AN: 242900Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133366
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1460032Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12AN XY: 726342
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74344
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2024 | The c.1271C>T (p.P424L) alteration is located in exon 4 (coding exon 4) of the SKI gene. This alteration results from a C to T substitution at nucleotide position 1271, causing the proline (P) at amino acid position 424 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 23, 2017 | The P424L variant in the SKI gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P424L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P424L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P424L as a variant of uncertain significance. - |
Shprintzen-Goldberg syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 01, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at