rs3740321

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012330.4(KAT6B):c.4495G>A(p.Val1499Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0178 in 1,614,038 control chromosomes in the GnomAD database, including 685 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1499T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.032 ( 142 hom., cov: 32)

Exomes 𝑓: 0.016 ( 543 hom. )

Consequence

KAT6B
NM_012330.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 6.03

Publications

15 publications found

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]

KAT6B Gene-Disease associations (from GenCC):

blepharophimosis - intellectual disability syndrome, SBBYS type
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
genitopatellar syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
KAT6B-related multiple congenital anomalies syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
RASopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

KAT6B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019197166).

BP6

Variant 10-75029319-G-A is Benign according to our data. Variant chr10-75029319-G-A is described in ClinVar as Benign. ClinVar VariationId is 260246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT6B	NM_012330.4 link	c.4495G>A	p.Val1499Ile	missense_variant	Exon 18 of 18	ENST00000287239.10	NP_036462.2	Q8WYB5-1B2RWN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT6B	ENST00000287239.10 link	c.4495G>A	p.Val1499Ile	missense_variant	Exon 18 of 18	1	NM_012330.4	ENSP00000287239.4		Q8WYB5-1

Frequencies

GnomAD3 genomes

AF:

0.0324

AC:

4920

AN:

152032

Hom.:

142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0576

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0446

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.0821

Gnomad SAS

AF:

0.0285

Gnomad FIN

AF:

0.0332

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.0335

GnomAD2 exomes

AF:

0.0349

AC:

8755

AN:

251050

AF XY:

0.0316

show subpopulations

Gnomad AFR exome

AF:

0.0567

Gnomad AMR exome

AF:

0.0853

Gnomad ASJ exome

AF:

0.0216

Gnomad EAS exome

AF:

0.0854

Gnomad FIN exome

AF:

0.0324

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.0341

GnomAD4 exome

AF:

0.0163

AC:

23770

AN:

1461888

Hom.:

543

Cov.:

AF XY:

0.0163

AC XY:

11825

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.0636

AC:

2129

AN:

33480

American (AMR)

AF:

0.0781

AC:

3491

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0235

AC:

613

AN:

26136

East Asian (EAS)

AF:

0.0679

AC:

2697

AN:

39700

South Asian (SAS)

AF:

0.0257

AC:

2217

AN:

86256

European-Finnish (FIN)

AF:

0.0316

AC:

1689

AN:

53416

Middle Eastern (MID)

AF:

0.0602

AC:

347

AN:

5768

European-Non Finnish (NFE)

AF:

0.00825

AC:

9172

AN:

1112012

Other (OTH)

AF:

0.0234

AC:

1415

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

1726

3451

5177

6902

8628

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.0323

AC:

4922

AN:

152150

Hom.:

142

Cov.:

AF XY:

0.0337

AC XY:

2508

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0576

AC:

2388

AN:

41460

American (AMR)

AF:

0.0444

AC:

680

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0222

AC:

AN:

3468

East Asian (EAS)

AF:

0.0821

AC:

424

AN:

5166

South Asian (SAS)

AF:

0.0283

AC:

136

AN:

4810

European-Finnish (FIN)

AF:

0.0332

AC:

352

AN:

10608

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0114

AC:

773

AN:

68014

Other (OTH)

AF:

0.0326

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

235

470

705

940

1175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0194

Hom.:

238

Bravo

AF:

0.0366

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.0486

AC:

214

ESP6500EA

AF:

0.0123

AC:

106

ExAC

AF:

0.0327

AC:

3967

Asia WGS

AF:

0.0580

AC:

200

AN:

3478

EpiCase

AF:

0.0141

EpiControl

AF:

0.0147

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Nov 11, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 05, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genitopatellar syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.097

T;.;T;.;.;.;.;T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.75

MetaRNN

Benign

0.0019

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.7

L;.;L;.;.;.;.;L;.

PhyloP100

6.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.52

.;.;.;N;.;.;N;N;N

REVEL

Benign

0.21

Sift

Benign

0.072

.;.;.;T;.;.;T;T;T

Sift4G

Benign

0.21

.;.;.;T;.;.;T;T;T

Polyphen

0.017

B;B;B;B;B;B;B;B;B

Vest4

0.086, 0.090, 0.057, 0.012

MPC

0.17

ClinPred

0.027

GERP RS

4.8

Varity_R

0.060

gMVP

0.029

Mutation Taster

=97/3

polymorphism (auto)

(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