rs114345135
Positions:
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_003036.4(SKI):c.1446G>A(p.Ala482=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00839 in 1,612,576 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0056 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0087 ( 60 hom. )
Consequence
SKI
NM_003036.4 synonymous
NM_003036.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.23
Genes affected
SKI (HGNC:10896): (SKI proto-oncogene) This gene encodes the nuclear protooncogene protein homolog of avian sarcoma viral (v-ski) oncogene. It functions as a repressor of TGF-beta signaling, and may play a role in neural tube development and muscle differentiation. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 1-2304074-G-A is Benign according to our data. Variant chr1-2304074-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 139115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-2304074-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-3.23 with no splicing effect.
BS2
?
High AC in GnomAd4 at 847 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SKI | NM_003036.4 | c.1446G>A | p.Ala482= | synonymous_variant | 4/7 | ENST00000378536.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SKI | ENST00000378536.5 | c.1446G>A | p.Ala482= | synonymous_variant | 4/7 | 1 | NM_003036.4 | P1 | |
SKI | ENST00000507179.1 | n.429G>A | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00557 AC: 848AN: 152214Hom.: 4 Cov.: 32
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GnomAD3 exomes AF: 0.00568 AC: 1397AN: 245914Hom.: 11 AF XY: 0.00546 AC XY: 731AN XY: 133790
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GnomAD4 exome AF: 0.00868 AC: 12679AN: 1460244Hom.: 60 Cov.: 32 AF XY: 0.00851 AC XY: 6180AN XY: 726416
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GnomAD4 genome ? AF: 0.00556 AC: 847AN: 152332Hom.: 4 Cov.: 32 AF XY: 0.00517 AC XY: 385AN XY: 74486
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 21, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 13, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 29, 2014 | 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. - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Shprintzen-Goldberg syndrome Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 03, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 13, 2023 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 15, 2016 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | SKI: BP4, BP7, BS2 - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at