rs141862996
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_003036.4(SKI):c.1196C>T(p.Ala399Val) variant causes a missense change. The variant allele was found at a frequency of 0.000296 in 1,613,072 control chromosomes in the GnomAD database, including 4 homozygotes. 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. A399A) 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.1196C>T | p.Ala399Val | missense_variant | 3/7 | ENST00000378536.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SKI | ENST00000378536.5 | c.1196C>T | p.Ala399Val | missense_variant | 3/7 | 1 | NM_003036.4 | P1 | |
SKI | ENST00000704337.1 | n.364C>T | non_coding_transcript_exon_variant | 3/4 | |||||
SKI | ENST00000478223.2 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00139 AC: 211AN: 152212Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.000375 AC: 94AN: 250702Hom.: 0 AF XY: 0.000251 AC XY: 34AN XY: 135598
GnomAD4 exome AF: 0.000183 AC: 267AN: 1460742Hom.: 2 Cov.: 32 AF XY: 0.000161 AC XY: 117AN XY: 726720
GnomAD4 genome ? AF: 0.00138 AC: 210AN: 152330Hom.: 2 Cov.: 32 AF XY: 0.00125 AC XY: 93AN XY: 74498
ClinVar
Submissions by phenotype
Shprintzen-Goldberg syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago | Aug 01, 2017 | SKI NM_003036.3 exon3 p.Ala399Val (c.1196C>T): This variant has not been reported in the literature but is present in 0.4% (117/24020) of African individuals, including 1 homozygote in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs141862996). This variant is present in ClinVar (Variation ID:213692). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 10, 2023 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 04, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 16, 2020 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 12, 2019 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at