chr12-88507036-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000899.5(KITLG):c.706T>C(p.Tyr236His) variant causes a missense change. The variant allele was found at a frequency of 0.00000319 in 1,569,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Y236Y) has been classified as Likely benign.
Frequency
Consequence
NM_000899.5 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 |
---|---|---|---|---|---|---|---|
KITLG | NM_000899.5 | c.706T>C | p.Tyr236His | missense_variant | 7/10 | ENST00000644744.1 | |
KITLG | NM_003994.6 | c.622T>C | p.Tyr208His | missense_variant | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KITLG | ENST00000644744.1 | c.706T>C | p.Tyr236His | missense_variant | 7/10 | NM_000899.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250754Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135520
GnomAD4 exome AF: 0.00000282 AC: 4AN: 1417276Hom.: 0 Cov.: 26 AF XY: 0.00000141 AC XY: 1AN XY: 708094
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74376
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 02, 2022 | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 236 of the KITLG protein (p.Tyr236His). This variant is present in population databases (rs761107987, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with KITLG-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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