8-41932227-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006766.5(KAT6A):ā€‹c.5993A>Gā€‹(p.Asn1998Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000286 in 1,607,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.000029 ( 0 hom. )

Consequence

KAT6A
NM_006766.5 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.92
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.25354227).
BS2
High AC in GnomAdExome4 at 42 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KAT6ANM_006766.5 linkc.5993A>G p.Asn1998Ser missense_variant 17/17 ENST00000265713.8 NP_006757.2 Q92794A5PKX7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KAT6AENST00000265713.8 linkc.5993A>G p.Asn1998Ser missense_variant 17/171 NM_006766.5 ENSP00000265713.2 Q92794
KAT6AENST00000406337.6 linkc.5999A>G p.Asn2000Ser missense_variant 18/185 ENSP00000385888.2 A0A3F2YNX6
KAT6AENST00000396930.4 linkc.5993A>G p.Asn1998Ser missense_variant 18/185 ENSP00000380136.3 Q92794
KAT6AENST00000649817.1 linkc.4673A>G p.Asn1558Ser missense_variant 11/11 ENSP00000497780.1 A0A3B3ITI3

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152220
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000163
AC:
4
AN:
246138
Hom.:
0
AF XY:
0.0000226
AC XY:
3
AN XY:
133032
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000360
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000289
AC:
42
AN:
1455372
Hom.:
0
Cov.:
32
AF XY:
0.0000263
AC XY:
19
AN XY:
723566
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000361
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152220
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 05, 2024This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1998 of the KAT6A protein (p.Asn1998Ser). This variant is present in population databases (rs778809488, gnomAD 0.003%). 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
22
DANN
Benign
0.94
DEOGEN2
Uncertain
0.47
.;T;T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
0.99
D;.;D
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.25
T;T;T
MetaSVM
Uncertain
-0.20
T
MutationAssessor
Benign
0.81
.;L;L
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-3.0
.;D;D
REVEL
Benign
0.17
Sift
Uncertain
0.0020
.;D;D
Sift4G
Uncertain
0.0090
.;D;D
Polyphen
1.0
.;D;D
Vest4
0.72, 0.38
MutPred
0.18
.;Gain of glycosylation at N1998 (P = 0.0041);Gain of glycosylation at N1998 (P = 0.0041);
MVP
0.42
MPC
0.15
ClinPred
0.27
T
GERP RS
5.8
Varity_R
0.32
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs778809488; hg19: chr8-41789745; API