rs113195648

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006766.5(KAT6A):c.4324G>A(p.Ala1442Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,614,088 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 4 hom., cov: 32)

Exomes 𝑓: 0.010 ( 99 hom. )

Consequence

KAT6A
NM_006766.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 3.16

Publications

8 publications found

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]

KAT6A Gene-Disease associations (from GenCC):

autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Illumina, PanelApp Australia, Labcorp Genetics (formerly Invitae)
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

KAT6A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064100027).

BP6

Variant 8-41933896-C-T is Benign according to our data. Variant chr8-41933896-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1088 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT6A	NM_006766.5 link	c.4324G>A	p.Ala1442Thr	missense_variant	Exon 17 of 17	ENST00000265713.8	NP_006757.2	Q92794A5PKX7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT6A	ENST00000265713.8 link	c.4324G>A	p.Ala1442Thr	missense_variant	Exon 17 of 17	1	NM_006766.5	ENSP00000265713.2		Q92794

Frequencies

GnomAD3 genomes

AF:

0.00715

AC:

1088

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0109

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00754

AC:

1891

AN:

250940

AF XY:

0.00775

show subpopulations

Gnomad AFR exome

AF:

0.00247

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.00517

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.0114

Gnomad OTH exome

AF:

0.00736

GnomAD4 exome

AF:

0.0104

AC:

15248

AN:

1461836

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

7489

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00215

AC:

AN:

33480

American (AMR)

AF:

0.00208

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00451

AC:

118

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00547

AC:

472

AN:

86258

European-Finnish (FIN)

AF:

0.0125

AC:

667

AN:

53390

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0120

AC:

13334

AN:

1111984

Other (OTH)

AF:

0.00786

AC:

475

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

882

1764

2647

3529

4411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

490

980

1470

1960

2450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00715

AC:

1088

AN:

152252

Hom.:

Cov.:

AF XY:

0.00666

AC XY:

496

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

41560

American (AMR)

AF:

0.00255

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00228

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0109

AC:

116

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0122

AC:

828

AN:

68014

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

106

160

213

266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00980

Hom.:

Bravo

AF:

0.00612

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0142

AC:

122

ExAC

AF:

0.00752

AC:

913

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0113

EpiControl

AF:

0.0106

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KAT6A: BP4, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 27, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 18, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jun 25, 2019

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome

Benign:1

Dec 30, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Apr 26, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.079

.;T;T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.83

T;.;T;D

MetaRNN

Benign

0.0064

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

.;L;L;.

PhyloP100

3.2

PrimateAI

Benign

0.46

PROVEAN

Benign

0.47

.;N;N;.

REVEL

Benign

0.11

Sift

Benign

1.0

.;T;T;.

Sift4G

Benign

0.87

.;T;T;.

Polyphen

0.51

.;P;P;.

Vest4

0.15, 0.14

MVP

0.38

MPC

0.18

ClinPred

0.012

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.055

gMVP

0.18

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over