1-2303937-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_003036.4(SKI):c.1309G>A(p.Ala437Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000249 in 1,611,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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. A437A) 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 -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SKI | NM_003036.4 | c.1309G>A | p.Ala437Thr | missense_variant | 4/7 | ENST00000378536.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SKI | ENST00000378536.5 | c.1309G>A | p.Ala437Thr | missense_variant | 4/7 | 1 | NM_003036.4 | P1 | |
SKI | ENST00000507179.1 | n.292G>A | non_coding_transcript_exon_variant | 1/2 | 2 | ||||
SKI | ENST00000704337.1 | downstream_gene_variant |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152144Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000158 AC: 38AN: 240356Hom.: 0 AF XY: 0.000114 AC XY: 15AN XY: 132114
GnomAD4 exome AF: 0.000264 AC: 386AN: 1459380Hom.: 0 Cov.: 32 AF XY: 0.000249 AC XY: 181AN XY: 726020
GnomAD4 genome AF: 0.000105 AC: 16AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74316
ClinVar
Submissions by phenotype
Shprintzen-Goldberg syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | SKI: BP4 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 11, 2019 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 20, 2019 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at