rs548231613

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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

Publications

1 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 -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 Benign/Likely_benign. ClinVar VariationId 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

GnomAD2 exomes

AF:

0.000884

AC:

196

AN:

221694

AF XY:

0.000801

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 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

African (AFR)

AF:

0.000210

AC:

AN:

33296

American (AMR)

AF:

0.000991

AC:

AN:

43390

Ashkenazi Jewish (ASJ)

AF:

0.000271

AC:

AN:

25842

East Asian (EAS)

AF:

0.000254

AC:

AN:

39388

South Asian (SAS)

AF:

0.0000118

AC:

AN:

85018

European-Finnish (FIN)

AF:

0.000375

AC:

AN:

47970

Middle Eastern (MID)

AF:

0.000227

AC:

AN:

4414

European-Non Finnish (NFE)

AF:

0.00159

AC:

1754

AN:

1106148

Other (OTH)

AF:

0.00129

AC:

AN:

59820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

105

211

316

422

527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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

AF:

0.000942

AC:

143

AN:

151856

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

AN XY:

74220

show subpopulations

African (AFR)

AF:

0.0000967

AC:

AN:

41382

American (AMR)

AF:

0.00105

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.000388

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00177

AC:

120

AN:

67898

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

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 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 -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

PhyloP100

4.0

Mutation Taster

=197/3

polymorphism

(source)

Splicing

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over