chr4-54658028-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_000222.3(KIT):c.14G>C(p.Arg5Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,600 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R5C) 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.14G>C | p.Arg5Pro | missense_variant | 1/21 | ENST00000288135.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIT | ENST00000288135.6 | c.14G>C | p.Arg5Pro | missense_variant | 1/21 | 1 | NM_000222.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461600Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727120
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 5 of the KIT protein (p.Arg5Pro). 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline 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: 951561). This variant has not been reported in the literature in individuals affected with KIT-related conditions. This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at