4-54695550-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_000222.3(KIT):c.106C>T(p.Pro36Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,066 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P36T) has been classified as Uncertain significance.
Frequency
Consequence
NM_000222.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIT | NM_000222.3 | c.106C>T | p.Pro36Ser | missense_variant | 2/21 | ENST00000288135.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIT | ENST00000288135.6 | c.106C>T | p.Pro36Ser | missense_variant | 2/21 | 1 | NM_000222.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251170Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135730
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461872Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727236
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74334
ClinVar
Submissions by phenotype
KIT-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 09, 2022 | The KIT c.106C>T variant is predicted to result in the amino acid substitution p.Pro36Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-55561716-C-T) and interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/528585/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 21, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 07, 2024 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 36 of the KIT protein (p.Pro36Ser). This variant is present in population databases (rs781633384, 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: 528585). 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