rs761598652

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PM2BP4_ModerateBP6_Very_Strong

The NM_006766.5(KAT6A):c.3742G>A(p.Glu1248Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

KAT6A
NM_006766.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.36

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Illumina, PanelApp Australia, Labcorp Genetics (formerly Invitae)
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

KAT6A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.098746955).

BP6

Variant 8-41934478-C-T is Benign according to our data. Variant chr8-41934478-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 377054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT6A	NM_006766.5 link	c.3742G>A	p.Glu1248Lys	missense_variant	Exon 17 of 17	ENST00000265713.8	NP_006757.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT6A	ENST00000265713.8 link	c.3742G>A	p.Glu1248Lys	missense_variant	Exon 17 of 17	1	NM_006766.5	ENSP00000265713.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000126

AC:

AN:

238566

AF XY:

0.00000775

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000911

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1457374

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724572

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33412

American (AMR)

AF:

0.0000690

AC:

AN:

43482

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26074

East Asian (EAS)

AF:

0.00

AC:

AN:

39626

South Asian (SAS)

AF:

0.00

AC:

AN:

85924

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53172

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109660

Other (OTH)

AF:

0.00

AC:

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 03, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.085

.;T;T;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.86

D;.;D;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.099

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

.;L;L;.

PhyloP100

2.4

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.93

.;N;N;.

REVEL

Benign

0.15

Sift

Benign

0.44

.;T;T;.

Sift4G

Benign

0.57

.;T;T;.

Polyphen

0.020

.;B;B;.

Vest4

0.13, 0.14

MutPred

0.26

.;Gain of ubiquitination at E1248 (P = 0.0114);Gain of ubiquitination at E1248 (P = 0.0114);Gain of ubiquitination at E1248 (P = 0.0114);

MVP

0.29

MPC

0.21

ClinPred

0.096

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.075

gMVP

0.11

Mutation Taster

=96/4

polymorphism

(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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over