dbSNP rs548231613: KAT6A:p.Gln1681_Gln1684del (chr8-41933168-CTGCGGCTGCTGT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM4BP6_Very_StrongBS2

The NM_006766.5(KAT6A):c.5040_5051delACAGCAGCCGCA(p.Gln1681_Gln1684del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00129 in 1,597,142 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00094 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0013 ( 5 hom. )

Consequence

KAT6A
NM_006766.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.99

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 -10 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_006766.5.

BP6

Variant 8-41933168-CTGCGGCTGCTGT-C is Benign according to our data. Variant chr8-41933168-CTGCGGCTGCTGT-C is described in ClinVar as [Likely_benign]. Clinvar id is 589281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 143 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT6A	NM_006766.5 link	c.5040_5051delACAGCAGCCGCA	p.Gln1681_Gln1684del	disruptive_inframe_deletion	Exon 17 of 17	ENST00000265713.8	NP_006757.2	Q92794A5PKX7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT6A	ENST00000265713.8 link	c.5040_5051delACAGCAGCCGCA	p.Gln1681_Gln1684del	disruptive_inframe_deletion	Exon 17 of 17	1	NM_006766.5	ENSP00000265713.2		Q92794

Frequencies

GnomAD3 genomes

AF:

0.000942

AC:

143

AN:

151738

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000969

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00177

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000884

AC:

196

AN:

221694

Hom.:

AF XY:

0.000801

AC XY:

AN XY:

119818

show subpopulations

Gnomad AFR exome

AF:

0.0000728

Gnomad AMR exome

AF:

0.000931

Gnomad ASJ exome

AF:

0.000212

Gnomad EAS exome

AF:

0.000709

Gnomad SAS exome

AF:

0.0000349

Gnomad FIN exome

AF:

0.000300

Gnomad NFE exome

AF:

0.00138

Gnomad OTH exome

AF:

0.00162

GnomAD4 exome

AF:

0.00133

AC:

1918

AN:

1445286

Hom.:

AF XY:

0.00128

AC XY:

917

AN XY:

717976

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.000991

Gnomad4 ASJ exome

AF:

0.000271

Gnomad4 EAS exome

AF:

0.000254

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.000375

Gnomad4 NFE exome

AF:

0.00159

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.000942

AC:

143

AN:

151856

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.0000967

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00177

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.000941

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KAT6A: BS1 -

not specified

Benign:1

Jul 30, 2018

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome

Benign:1

May 28, 2019

Mendelics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Dec 07, 2018

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Splicing

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