8-41932259-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_006766.5(KAT6A):c.5961G>A(p.Met1987Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,430 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 (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
KAT6A
NM_006766.5 missense
NM_006766.5 missense
Scores
2
5
7
Clinical Significance
Conservation
PhyloP100: 4.37
Genes affected
KAT6A (HGNC:13013): (lysine acetyltransferase 6A) This gene encodes a member of the MOZ, YBFR2, SAS2, TIP60 family of histone acetyltransferases. The protein is composed of a nuclear localization domain, a double C2H2 zinc finger domain that binds to acetylated histone tails, a histone acetyl-transferase domain, a glutamate/aspartate-rich region, and a serine- and methionine-rich transactivation domain. It is part of a complex that acetylates lysine-9 residues in histone 3, and in addition, it acts as a co-activator for several transcription factors. Allelic variants of this gene are associated with an autosomal dominant form of cognitive disability. Chromosomal translocations of this gene are associated with acute myeloid leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, KAT6A
BP4
?
Computational evidence support a benign effect (MetaRNN=0.35654068).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KAT6A | NM_006766.5 | c.5961G>A | p.Met1987Ile | missense_variant | 17/17 | ENST00000265713.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KAT6A | ENST00000265713.8 | c.5961G>A | p.Met1987Ile | missense_variant | 17/17 | 1 | NM_006766.5 | A2 | |
KAT6A | ENST00000406337.6 | c.5967G>A | p.Met1989Ile | missense_variant | 18/18 | 5 | A2 | ||
KAT6A | ENST00000396930.4 | c.5961G>A | p.Met1987Ile | missense_variant | 18/18 | 5 | A2 | ||
KAT6A | ENST00000649817.1 | c.4644G>A | p.Met1548Ile | missense_variant | 11/11 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461430Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727010
GnomAD4 exome
AF:
AC:
1
AN:
1461430
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
727010
Gnomad4 AFR exome
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Gnomad4 ASJ exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 08, 2023 | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1987 of the KAT6A protein (p.Met1987Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KAT6A-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
REVEL
Benign
Polyphen
0.94
.;P;P
Vest4
0.64, 0.65
MutPred
0.22
.;Loss of MoRF binding (P = 0.0731);Loss of MoRF binding (P = 0.0731);
MVP
MPC
0.21
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.