1-2304437-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_003036.4(SKI):c.1619C>T(p.Ala540Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000404 in 1,560,528 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. A540A) 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 -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SKI | NM_003036.4 | c.1619C>T | p.Ala540Val | missense_variant | 5/7 | ENST00000378536.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SKI | ENST00000378536.5 | c.1619C>T | p.Ala540Val | missense_variant | 5/7 | 1 | NM_003036.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152210Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000178 AC: 3AN: 168448Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 89850
GnomAD4 exome AF: 0.0000405 AC: 57AN: 1408200Hom.: 0 Cov.: 34 AF XY: 0.0000374 AC XY: 26AN XY: 696000
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152328Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74488
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 08, 2024 | The c.1619C>T (p.A540V) alteration is located in exon 5 (coding exon 5) of the SKI gene. This alteration results from a C to T substitution at nucleotide position 1619, causing the alanine (A) at amino acid position 540 to be replaced by a valine (V). 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 | Jun 23, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Shprintzen-Goldberg syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 22, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at