rs144417514

Positions:

chr8-41933268-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006766.5(KAT6A):c.4952C>T(p.Pro1651Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 1,565,254 control chromosomes in the GnomAD database, including 3 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 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 3 hom. )

Consequence

KAT6A
NM_006766.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.516

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0101650655).

BP6

Variant 8-41933268-G-A is Benign according to our data. Variant chr8-41933268-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-41933268-G-A is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 206 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT6A	NM_006766.5 link	c.4952C>T	p.Pro1651Leu	missense_variant	17/17	ENST00000265713.8	NP_006757.2	Q92794A5PKX7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT6A	ENST00000265713.8 link	c.4952C>T	p.Pro1651Leu	missense_variant	17/17	1	NM_006766.5	ENSP00000265713.2		Q92794

Frequencies

GnomAD3 genomes

AF:

0.00136

AC:

206

AN:

151584

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00204

Gnomad ASJ

AF:

0.000578

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00211

Gnomad OTH

AF:

0.000483

GnomAD3 exomes

AF:

0.00124

AC:

229

AN:

183942

Hom.:

AF XY:

0.00114

AC XY:

113

AN XY:

98968

show subpopulations

Gnomad AFR exome

AF:

0.000326

Gnomad AMR exome

AF:

0.000439

Gnomad ASJ exome

AF:

0.000941

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00205

Gnomad NFE exome

AF:

0.00223

Gnomad OTH exome

AF:

0.000616

GnomAD4 exome

AF:

0.00177

AC:

2505

AN:

1413558

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

1180

AN XY:

699934

show subpopulations

Gnomad4 AFR exome

AF:

0.000548

Gnomad4 AMR exome

AF:

0.000585

Gnomad4 ASJ exome

AF:

0.000779

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000248

Gnomad4 FIN exome

AF:

0.00182

Gnomad4 NFE exome

AF:

0.00210

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.00136

AC:

206

AN:

151696

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

74152

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.000578

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00211

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.00190

Hom.:

Bravo

AF:

0.00155

ESP6500AA

AF:

0.000471

AC:

ESP6500EA

AF:

0.00171

AC:

ExAC

AF:

0.000852

AC:

102

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:7

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 20, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	KAT6A: BS1 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 2018	- -

KAT6A-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 29, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2018

This alteration is classified as likely 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

0.12

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.11

.;T;T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.59

T;.;T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.010

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.81

.;L;L;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.4

N;N;N;.

REVEL

Benign

0.035

Sift

Uncertain

0.0060

D;D;D;.

Sift4G

Benign

0.075

.;T;T;.

Polyphen

0.10

.;B;B;.

Vest4

0.39, 0.36

MVP

0.29

MPC

0.19

ClinPred

0.010

GERP RS

3.5

Varity_R

0.070

gMVP

0.11

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