rs3740321

Positions:

chr10-75029319-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The ENST00000287239.10(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. 14/20 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
ENST00000287239.10 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.03

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KAT6B. . Gene score misZ 2.8874 (greater than the threshold 3.09). Trascript score misZ 4.8748 (greater than threshold 3.09). GenCC has associacion of gene with RASopathy, genitopatellar syndrome, KAT6B-related multiple congenital anomalies syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type.

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 id is 260246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75029319-G-A is described in Lovd as [Benign]. Variant chr10-75029319-G-A is described in Lovd as [Likely_benign].

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/exons	MANE	Protein	UniProt
KAT6B	NM_012330.4 linkuse as main transcript	c.4495G>A	p.Val1499Ile	missense_variant	18/18	ENST00000287239.10	NP_036462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT6B	ENST00000287239.10 linkuse as main transcript	c.4495G>A	p.Val1499Ile	missense_variant	18/18	1	NM_012330.4	ENSP00000287239	P2	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

GnomAD3 exomes

AF:

0.0349

AC:

8755

AN:

251050

Hom.:

300

AF XY:

0.0316

AC XY:

4289

AN XY:

135714

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 SAS exome

AF:

0.0278

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

Gnomad4 AFR exome

AF:

0.0636

Gnomad4 AMR exome

AF:

0.0781

Gnomad4 ASJ exome

AF:

0.0235

Gnomad4 EAS exome

AF:

0.0679

Gnomad4 SAS exome

AF:

0.0257

Gnomad4 FIN exome

AF:

0.0316

Gnomad4 NFE exome

AF:

0.00825

Gnomad4 OTH exome

AF:

0.0234

GnomAD4 genome

AF:

0.0323

AC:

4922

AN:

152150

Hom.:

142

Cov.:

AF XY:

0.0337

AC XY:

2508

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0576

Gnomad4 AMR

AF:

0.0444

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.0821

Gnomad4 SAS

AF:

0.0283

Gnomad4 FIN

AF:

0.0332

Gnomad4 NFE

AF:

0.0114

Gnomad4 OTH

AF:

0.0326

Alfa

AF:

0.0181

Hom.:

117

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

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 11, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2016	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. -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Genitopatellar syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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

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;.

MutationTaster

Benign

1.0

P;P;P;P;P

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over