rs113195648

Positions:

chr8-41933896-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_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. 13/20 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KAT6A. . Gene score misZ 2.0718 (greater than the threshold 3.09). Trascript score misZ 3.1208 (greater than threshold 3.09). GenCC has associacion of gene with syndromic intellectual disability, autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome.

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 [Likely_benign]. Clinvar id 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/exons	MANE	Protein	UniProt
KAT6A	NM_006766.5 linkuse as main transcript	c.4324G>A	p.Ala1442Thr	missense_variant	17/17	ENST00000265713.8	NP_006757.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT6A	ENST00000265713.8 linkuse as main transcript	c.4324G>A	p.Ala1442Thr	missense_variant	17/17	1	NM_006766.5	ENSP00000265713	A2

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

GnomAD3 exomes

AF:

0.00754

AC:

1891

AN:

250940

Hom.:

AF XY:

0.00775

AC XY:

1052

AN XY:

135666

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 SAS exome

AF:

0.00520

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

Gnomad4 AFR exome

AF:

0.00215

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.00451

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00547

Gnomad4 FIN exome

AF:

0.0125

Gnomad4 NFE exome

AF:

0.0120

Gnomad4 OTH exome

AF:

0.00786

GnomAD4 genome

AF:

0.00715

AC:

1088

AN:

152252

Hom.:

Cov.:

AF XY:

0.00666

AC XY:

496

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0109

Gnomad4 NFE

AF:

0.0122

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.0103

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

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 18, 2017	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	KAT6A: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 27, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 25, 2019

- -

Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Dec 30, 2021

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2016

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

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;.

MutationTaster

Benign

0.99

D;D;D

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

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