rs3740322

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012330.4(KAT6B):c.4278C>T(p.Ala1426=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 1,614,018 control chromosomes in the GnomAD database, including 685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 141 hom., cov: 32)

Exomes 𝑓: 0.016 ( 544 hom. )

Consequence

KAT6B
NM_012330.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.03

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 10-75029102-C-T is Benign according to our data. Variant chr10-75029102-C-T is described in ClinVar as [Benign]. Clinvar id is 260245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75029102-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.076 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAT6B	NM_012330.4 linkuse as main transcript	c.4278C>T	p.Ala1426=	synonymous_variant	18/18	ENST00000287239.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAT6B	ENST00000287239.10 linkuse as main transcript	c.4278C>T	p.Ala1426=	synonymous_variant	18/18	1	NM_012330.4	P2	Q8WYB5-1

Frequencies

GnomAD3 genomes

AF:

0.0325

AC:

4936

AN:

152018

Hom.:

141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0577

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0448

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.0824

Gnomad SAS

AF:

0.0286

Gnomad FIN

AF:

0.0335

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.0335

GnomAD3 exomes

AF:

0.0349

AC:

8780

AN:

251296

Hom.:

300

AF XY:

0.0317

AC XY:

4307

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.0568

Gnomad AMR exome

AF:

0.0853

Gnomad ASJ exome

AF:

0.0216

Gnomad EAS exome

AF:

0.0854

Gnomad SAS exome

AF:

0.0284

Gnomad FIN exome

AF:

0.0324

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.0339

GnomAD4 exome

AF:

0.0163

AC:

23832

AN:

1461882

Hom.:

544

Cov.:

AF XY:

0.0163

AC XY:

11865

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0635

Gnomad4 AMR exome

AF:

0.0781

Gnomad4 ASJ exome

AF:

0.0235

Gnomad4 EAS exome

AF:

0.0679

Gnomad4 SAS exome

AF:

0.0263

Gnomad4 FIN exome

AF:

0.0316

Gnomad4 NFE exome

AF:

0.00826

Gnomad4 OTH exome

AF:

0.0235

GnomAD4 genome

AF:

0.0325

AC:

4938

AN:

152136

Hom.:

141

Cov.:

AF XY:

0.0338

AC XY:

2512

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0577

Gnomad4 AMR

AF:

0.0446

Gnomad4 ASJ

AF:

0.0219

Gnomad4 EAS

AF:

0.0824

Gnomad4 SAS

AF:

0.0285

Gnomad4 FIN

AF:

0.0335

Gnomad4 NFE

AF:

0.0114

Gnomad4 OTH

AF:

0.0327

Alfa

AF:

0.0195

Hom.:

Bravo

AF:

0.0366

Asia WGS

AF:

0.0580

AC:

201

AN:

3478

EpiCase

AF:

0.0141

EpiControl

AF:

0.0147

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 11, 2023	- -
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:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Genitopatellar syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

Cadd

Benign

0.020

Dann

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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