10-74842984-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012330.4(KAT6B):​c.127G>A​(p.Asp43Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

KAT6B
NM_012330.4 missense

Scores

4
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60
Variant links:
Genes affected
KAT6B (HGNC:17582): (lysine acetyltransferase 6B) The protein encoded by this gene is a histone acetyltransferase and component of the MOZ/MORF protein complex. In addition to its acetyltransferase activity, the encoded protein has transcriptional activation activity in its N-terminal end and transcriptional repression activity in its C-terminal end. This protein is necessary for RUNX2-dependent transcriptional activation and could be involved in brain development. Mutations have been found in patients with genitopatellar syndrome. A translocation of this gene and the CREBBP gene results in acute myeloid leukemias. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

Genome browser will be placed here

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;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KAT6BNM_012330.4 linkc.127G>A p.Asp43Asn missense_variant Exon 3 of 18 ENST00000287239.10 NP_036462.2 Q8WYB5-1B2RWN8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KAT6BENST00000287239.10 linkc.127G>A p.Asp43Asn missense_variant Exon 3 of 18 1 NM_012330.4 ENSP00000287239.4 Q8WYB5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Genitopatellar syndrome Uncertain:1
May 14, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 43 of the KAT6B protein (p.Asp43Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KAT6B-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KAT6B protein function. 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
Uncertain
0.38
BayesDel_addAF
Benign
-0.046
T
BayesDel_noAF
Benign
-0.30
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.46
T;.;.;T;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.;.;.;.;.
Eigen
Pathogenic
0.93
Eigen_PC
Pathogenic
0.94
FATHMM_MKL
Pathogenic
1.0
D
M_CAP
Benign
0.040
D
MetaRNN
Uncertain
0.52
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.22
D
MutationAssessor
Uncertain
2.2
M;.;M;M;M;.;.;.;.;.;M;.;M;.;M;M;.;.;.;.;.;.;M;.
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-3.9
.;.;.;.;D;.;.;.;.;.;.;.;D;.;D;D;.;.;.;.;.;.;D;.
REVEL
Uncertain
0.41
Sift
Benign
0.088
.;.;.;.;T;.;.;.;.;.;.;.;T;.;T;D;.;.;.;.;.;.;T;.
Sift4G
Benign
0.074
.;.;.;.;T;.;.;.;.;.;.;.;T;.;T;T;.;.;.;.;.;.;T;.
Polyphen
1.0
D;.;D;D;D;.;.;.;.;.;D;.;D;.;D;D;.;.;.;.;.;.;D;.
Vest4
0.53, 0.55, 0.51, 0.57, 0.50
MutPred
0.20
Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP
0.82
MPC
0.98
ClinPred
0.99
D
GERP RS
6.1
Varity_R
0.23
gMVP
0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-76602742; API