chr4-54728031-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_000222.3(KIT):āc.1900C>Gā(p.Arg634Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R634Q) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIT | NM_000222.3 | c.1900C>G | p.Arg634Gly | missense_variant | 13/21 | ENST00000288135.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIT | ENST00000288135.6 | c.1900C>G | p.Arg634Gly | missense_variant | 13/21 | 1 | NM_000222.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152094Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251296Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135808
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461742Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727184
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152094Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74290
ClinVar
Submissions by phenotype
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 06, 2021 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with KIT-related conditions. This variant is present in population databases (rs144369407, ExAC 0.001%). This sequence change replaces arginine with glycine at codon 634 of the KIT protein (p.Arg634Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 24, 2023 | The p.R634G variant (also known as c.1900C>G), located in coding exon 13 of the KIT gene, results from a C to G substitution at nucleotide position 1900. The arginine at codon 634 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. 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