10-75022093-GGAGGAGGAAGAAGAGGAGGAAGAA-GGAGGAGGAAGAAGAGGAGGAAGAAGAGGAGGAAGAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_012330.4(KAT6B):c.3252_3263dupGGAAGAAGAGGA(p.Glu1085_Glu1088dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0000722 in 1,607,312 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_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. E1088E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

KAT6B
NM_012330.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

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 -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_012330.4

BP6

Variant 10-75022093-G-GGAGGAGGAAGAA is Benign according to our data. Variant chr10-75022093-G-GGAGGAGGAAGAA is described in ClinVar as Likely_benign. ClinVar VariationId is 1663325.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 57 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_3263dupGGAAGAAGAGGA	p.Glu1085_Glu1088dup	disruptive_inframe_insertion	Exon 16 of 18	NP_036462.2
KAT6B	NM_001370136.1		c.3252_3263dupGGAAGAAGAGGA	p.Glu1085_Glu1088dup	disruptive_inframe_insertion	Exon 16 of 18	NP_001357065.1
KAT6B	NM_001370137.1		c.3252_3263dupGGAAGAAGAGGA	p.Glu1085_Glu1088dup	disruptive_inframe_insertion	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_3263dupGGAAGAAGAGGA	p.Glu1085_Glu1088dup	disruptive_inframe_insertion	Exon 16 of 18	ENSP00000287239.4
KAT6B	ENST00000372711.2	TSL:1	c.2703_2714dupGGAAGAAGAGGA	p.Glu902_Glu905dup	disruptive_inframe_insertion	Exon 16 of 18	ENSP00000361796.1
KAT6B	ENST00000648725.1		c.3252_3263dupGGAAGAAGAGGA	p.Glu1085_Glu1088dup	disruptive_inframe_insertion	Exon 16 of 18	ENSP00000497841.1

Frequencies

GnomAD3 genomes

AF:

0.000376

AC:

AN:

151502

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000329

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000101

AC:

AN:

247568

AF XY:

0.0000820

show subpopulations

Gnomad AFR exome

AF:

0.00113

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000901

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000405

AC:

AN:

1455810

Hom.:

Cov.:

AF XY:

0.0000400

AC XY:

AN XY:

724312

show subpopulations

African (AFR)

AF:

0.000927

AC:

AN:

33432

American (AMR)

AF:

0.000112

AC:

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53026

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

1106714

Other (OTH)

AF:

0.000116

AC:

AN:

60238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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

AF:

0.000376

AC:

AN:

151502

Hom.:

Cov.:

AF XY:

0.000419

AC XY:

AN XY:

73972

show subpopulations

African (AFR)

AF:

0.00121

AC:

AN:

41212

American (AMR)

AF:

0.000329

AC:

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67796

Other (OTH)

AF:

0.000479

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.0000397

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Genitopatellar syndrome

Benign:1

Dec 07, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.8

Mutation Taster

=81/19

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