NM_012330.4:c.3252_3263delGGAAGAAGAGGA

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP3BP6_Very_StrongBS2

The NM_012330.4(KAT6B):c.3252_3263delGGAAGAAGAGGA(p.Glu1085_Glu1088del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00903 in 1,607,396 control chromosomes in the GnomAD database, including 85 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 (★★). Synonymous variant affecting the same amino acid position (i.e. E1084E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0071 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0092 ( 80 hom. )

Consequence

KAT6B
NM_012330.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 5.76

Publications

4 publications found

Variant links:

Genes affected

KAT6B (HGNC:17582): (lysine acetyltransferase 6B) The protein encoded by this gene is a histone acetyltransferase and component of the MOZ/MORF protein complex. In addition to its acetyltransferase activity, the encoded protein has transcriptional activation activity in its N-terminal end and transcriptional repression activity in its C-terminal end. This protein is necessary for RUNX2-dependent transcriptional activation and could be involved in brain development. Mutations have been found in patients with genitopatellar syndrome. A translocation of this gene and the CREBBP gene results in acute myeloid leukemias. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]

KAT6B Gene-Disease associations (from GenCC):

blepharophimosis - intellectual disability syndrome, SBBYS type
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
genitopatellar syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
KAT6B-related multiple congenital anomalies syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
RASopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

KAT6B links:

ENSG00000234149 (HGNC:):

ENSG00000234149 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_012330.4

BP6

Variant 10-75022093-GGAGGAGGAAGAA-G is Benign according to our data. Variant chr10-75022093-GGAGGAGGAAGAA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1069 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012330.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KAT6B	NM_012330.4	MANE Select	c.3252_3263delGGAAGAAGAGGA	p.Glu1085_Glu1088del	disruptive_inframe_deletion	Exon 16 of 18	NP_036462.2
KAT6B	NM_001370136.1		c.3252_3263delGGAAGAAGAGGA	p.Glu1085_Glu1088del	disruptive_inframe_deletion	Exon 16 of 18	NP_001357065.1
KAT6B	NM_001370137.1		c.3252_3263delGGAAGAAGAGGA	p.Glu1085_Glu1088del	disruptive_inframe_deletion	Exon 16 of 18	NP_001357066.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KAT6B	ENST00000287239.10	TSL:1 MANE Select	c.3252_3263delGGAAGAAGAGGA	p.Glu1085_Glu1088del	disruptive_inframe_deletion	Exon 16 of 18	ENSP00000287239.4
KAT6B	ENST00000372711.2	TSL:1	c.2703_2714delGGAAGAAGAGGA	p.Glu902_Glu905del	disruptive_inframe_deletion	Exon 16 of 18	ENSP00000361796.1
KAT6B	ENST00000648725.1		c.3252_3263delGGAAGAAGAGGA	p.Glu1085_Glu1088del	disruptive_inframe_deletion	Exon 16 of 18	ENSP00000497841.1

Frequencies

GnomAD3 genomes

AF:

0.00705

AC:

1068

AN:

151498

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00214

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00572

Gnomad ASJ

AF:

0.00491

Gnomad EAS

AF:

0.00927

Gnomad SAS

AF:

0.00354

Gnomad FIN

AF:

0.00485

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.00288

GnomAD2 exomes

AF:

0.00687

AC:

1700

AN:

247568

AF XY:

0.00704

show subpopulations

Gnomad AFR exome

AF:

0.00213

Gnomad AMR exome

AF:

0.00465

Gnomad ASJ exome

AF:

0.00481

Gnomad EAS exome

AF:

0.0119

Gnomad FIN exome

AF:

0.00470

Gnomad NFE exome

AF:

0.00891

Gnomad OTH exome

AF:

0.00528

GnomAD4 exome

AF:

0.00923

AC:

13443

AN:

1455780

Hom.:

AF XY:

0.00923

AC XY:

6686

AN XY:

724302

show subpopulations

African (AFR)

AF:

0.00191

AC:

AN:

33432

American (AMR)

AF:

0.00479

AC:

214

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.00536

AC:

140

AN:

26116

East Asian (EAS)

AF:

0.0108

AC:

427

AN:

39664

South Asian (SAS)

AF:

0.00352

AC:

303

AN:

86196

European-Finnish (FIN)

AF:

0.00517

AC:

274

AN:

53026

Middle Eastern (MID)

AF:

0.00382

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0104

AC:

11504

AN:

1106690

Other (OTH)

AF:

0.00822

AC:

495

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

649

1298

1946

2595

3244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.00705

AC:

1069

AN:

151616

Hom.:

Cov.:

AF XY:

0.00673

AC XY:

499

AN XY:

74098

show subpopulations

African (AFR)

AF:

0.00215

AC:

AN:

41334

American (AMR)

AF:

0.00571

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00491

AC:

AN:

3464

East Asian (EAS)

AF:

0.00929

AC:

AN:

5168

South Asian (SAS)

AF:

0.00354

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00485

AC:

AN:

10516

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0111

AC:

752

AN:

67784

Other (OTH)

AF:

0.00285

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

145

193

241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00500

Hom.:

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 03, 2016

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KAT6B: BS1, BS2

Sep 29, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 29, 2020

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.Glu1086_Glu1089del variant in KAT6B is classified as benign because it has been identified in 1.2% (237/19782) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA1.

Genitopatellar syndrome

Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Intellectual disability

Benign:1

Jan 01, 2019

Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.8

Mutation Taster

=173/27

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over