rs1016976398
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP2BP4
The NM_000222.3(KIT):c.1700A>G(p.Asn567Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,644 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. N567H) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIT | NM_000222.3 | c.1700A>G | p.Asn567Ser | missense_variant | 11/21 | ENST00000288135.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIT | ENST00000288135.6 | c.1700A>G | p.Asn567Ser | missense_variant | 11/21 | 1 | NM_000222.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461644Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727148
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Jun 28, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 28, 2023 | The p.N567S variant (also known as c.1700A>G), located in coding exon 11 of the KIT gene, results from an A to G substitution at nucleotide position 1700. The asparagine at codon 567 is replaced by serine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 567 of the KIT protein (p.Asn567Ser). This variant is not present in population databases (gnomAD no frequency). 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: 458888). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at