chr8-41932246-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_006766.5(KAT6A):c.5974G>C(p.Val1992Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V1992M) has been classified as Likely benign.
Frequency
Consequence
NM_006766.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KAT6A | NM_006766.5 | c.5974G>C | p.Val1992Leu | missense_variant | 17/17 | ENST00000265713.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KAT6A | ENST00000265713.8 | c.5974G>C | p.Val1992Leu | missense_variant | 17/17 | 1 | NM_006766.5 | A2 | |
KAT6A | ENST00000406337.6 | c.5980G>C | p.Val1994Leu | missense_variant | 18/18 | 5 | A2 | ||
KAT6A | ENST00000396930.4 | c.5974G>C | p.Val1992Leu | missense_variant | 18/18 | 5 | A2 | ||
KAT6A | ENST00000649817.1 | c.4657G>C | p.Val1553Leu | missense_variant | 11/11 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 20, 2018 | The V1992L variant in the KAT6A gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The V1992L variant is not observed in large population cohorts (Lek et al., 2016). The V1992L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret V1992L as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at