4-54737268-G-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM2PP2BP4_StrongBP6
The NM_000222.3(KIT):āc.2790G>Cā(p.Glu930Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E930K) has been classified as Uncertain significance.
Frequency
Consequence
NM_000222.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIT | NM_000222.3 | c.2790G>C | p.Glu930Asp | missense_variant | 20/21 | ENST00000288135.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIT | ENST00000288135.6 | c.2790G>C | p.Glu930Asp | missense_variant | 20/21 | 1 | NM_000222.3 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251090Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135698
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1458322Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2AN XY: 725778
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 10, 2023 | 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. 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 aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 570928). This variant has not been reported in the literature in individuals affected with KIT-related conditions. This variant is present in population databases (rs759076549, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 930 of the KIT protein (p.Glu930Asp). - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 08, 2022 | 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