rs386833402
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_000222.3(KIT):c.839C>T(p.Ala280Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,120 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★★).
Frequency
Consequence
NM_000222.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KIT | NM_000222.3 | c.839C>T | p.Ala280Val | missense_variant | 5/21 | ENST00000288135.6 | NP_000213.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KIT | ENST00000288135.6 | c.839C>T | p.Ala280Val | missense_variant | 5/21 | 1 | NM_000222.3 | ENSP00000288135.6 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 151958Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251286Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135806
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461162Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 726952
GnomAD4 genome AF: 0.0000329 AC: 5AN: 151958Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2AN XY: 74196
ClinVar
Submissions by phenotype
KIT-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 29, 2023 | The KIT c.839C>T variant is predicted to result in the amino acid substitution p.Ala280Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.025% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-55569972-C-T). This variant is classified as a uncertain variant in the ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/41605/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jul 13, 2012 | - - |
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 26, 2024 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 280 of the KIT protein (p.Ala280Val). This variant is present in population databases (rs386833402, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with KIT-related conditions. ClinVar contains an entry for this variant (Variation ID: 41605). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 08, 2024 | 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