10-75028886-AGAGGAGGAGGAG-AGAGGAGGAGGAGGAG

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.4077_4079dupGGA(p.Glu1360dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0000572 in 1,609,656 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. E1360E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000059 ( 1 hom. )

Consequence

KAT6B
NM_012330.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.23

Publications

1 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:

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 10-75028886-A-AGAG is Benign according to our data. Variant chr10-75028886-A-AGAG is described in ClinVar as Likely_benign. ClinVar VariationId is 509215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 6 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.4077_4079dupGGA	p.Glu1360dup	disruptive_inframe_insertion	Exon 18 of 18	NP_036462.2
KAT6B	NM_001370136.1		c.4077_4079dupGGA	p.Glu1360dup	disruptive_inframe_insertion	Exon 18 of 18	NP_001357065.1
KAT6B	NM_001370137.1		c.4077_4079dupGGA	p.Glu1360dup	disruptive_inframe_insertion	Exon 18 of 18	NP_001357066.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KAT6B	ENST00000287239.10	TSL:1 MANE Select	c.4077_4079dupGGA	p.Glu1360dup	disruptive_inframe_insertion	Exon 18 of 18	ENSP00000287239.4
KAT6B	ENST00000372711.2	TSL:1	c.3528_3530dupGGA	p.Glu1177dup	disruptive_inframe_insertion	Exon 18 of 18	ENSP00000361796.1
KAT6B	ENST00000648725.1		c.4077_4079dupGGA	p.Glu1360dup	disruptive_inframe_insertion	Exon 18 of 18	ENSP00000497841.1

Frequencies

GnomAD3 genomes

AF:

0.0000332

AC:

AN:

150732

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000122

AC:

AN:

245752

AF XY:

0.000128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000264

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000359

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000590

AC:

AN:

1458806

Hom.:

Cov.:

AF XY:

0.0000744

AC XY:

AN XY:

725894

show subpopulations

African (AFR)

AF:

0.000155

AC:

AN:

32270

American (AMR)

AF:

0.000202

AC:

AN:

44568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.000202

AC:

AN:

39690

South Asian (SAS)

AF:

0.000534

AC:

AN:

86116

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000810

AC:

AN:

1110722

Other (OTH)

AF:

0.000149

AC:

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000398

AC:

AN:

150850

Hom.:

Cov.:

AF XY:

0.0000678

AC XY:

AN XY:

73772

show subpopulations

African (AFR)

AF:

0.0000248

AC:

AN:

40272

American (AMR)

AF:

0.00

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.000623

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000728

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 25, 2017

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Genitopatellar syndrome

Benign:1

Aug 11, 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

4.2

Mutation Taster

=86/14

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