rs150934009
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_003036.4(SKI):c.1033G>A(p.Ala345Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000542 in 1,613,568 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A345A) 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 -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SKI | NM_003036.4 | c.1033G>A | p.Ala345Thr | missense_variant | 2/7 | ENST00000378536.5 | NP_003027.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SKI | ENST00000378536.5 | c.1033G>A | p.Ala345Thr | missense_variant | 2/7 | 1 | NM_003036.4 | ENSP00000367797 | P1 | |
SKI | ENST00000478223.2 | n.140G>A | non_coding_transcript_exon_variant | 2/3 | 3 | |||||
SKI | ENST00000704337.1 | n.201G>A | non_coding_transcript_exon_variant | 2/4 | ||||||
SKI | ENST00000508416.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000342 AC: 52AN: 152164Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000314 AC: 79AN: 251266Hom.: 0 AF XY: 0.000294 AC XY: 40AN XY: 135866
GnomAD4 exome AF: 0.000562 AC: 822AN: 1461404Hom.: 1 Cov.: 32 AF XY: 0.000528 AC XY: 384AN XY: 727002
GnomAD4 genome AF: 0.000342 AC: 52AN: 152164Hom.: 0 Cov.: 33 AF XY: 0.000363 AC XY: 27AN XY: 74330
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 04, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2021 | This alteration is classified as likely 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | SKI: BS1 - |
Shprintzen-Goldberg syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
SKI-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 21, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at