Variant 8-41934478-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_ModerateBP6_Moderate

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. 15/21 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, single submitter B:1

Conservation

PhyloP100: 2.36

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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=0.098746955).

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 id is 377054.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT6A	NM_006766.5 linkuse as main transcript	c.3742G>A	p.Glu1248Lys	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 linkuse as main transcript	c.3742G>A	p.Glu1248Lys	missense_variant	17/17	1	NM_006766.5	ENSP00000265713.2		Q92794

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000126

AC:

AN:

238566

Hom.:

AF XY:

0.00000775

AC XY:

AN XY:

129084

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 SAS 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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000690

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

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

Aug 03, 2016

- -

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

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;.

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

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