rs1060502570
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_000222.3(KIT):c.793G>A(p.Gly265Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G265A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000222.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIT | NM_000222.3 | c.793G>A | p.Gly265Ser | missense_variant | 5/21 | ENST00000288135.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIT | ENST00000288135.6 | c.793G>A | p.Gly265Ser | missense_variant | 5/21 | 1 | NM_000222.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 151910Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461538Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727058
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 151910Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74166
ClinVar
Submissions by phenotype
Gastrointestinal stromal tumor Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Sep 04, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 265 of the KIT protein (p.Gly265Ser). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 409795). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 15, 2023 | The p.G265S variant (also known as c.793G>A), located in coding exon 5 of the KIT gene, results from a G to A substitution at nucleotide position 793. The glycine at codon 265 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at