10-75022147-GGAAGAAGAAGAA-GGAAGAAGAAGAAGAAGAA

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP3BP6BS2

The NM_012330.4(KAT6B):c.3307_3312dupGAAGAA(p.Glu1103_Glu1104dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000374 in 1,605,900 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 22)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

KAT6B
NM_012330.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.08

Publications

23 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
multiple congenital anomalies/dysmorphic 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: Likely_benign. The variant received -6 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_012330.4

BP6

Variant 10-75022147-G-GGAAGAA is Benign according to our data. Variant chr10-75022147-G-GGAAGAA is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1388063.

BS2

High AC in GnomAdExome4 at 58 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	UniProt
KAT6B	NM_012330.4	MANE Select	c.3307_3312dupGAAGAA	p.Glu1103_Glu1104dup	conservative_inframe_insertion	Exon 16 of 18	NP_036462.2	Q8WYB5-1
KAT6B	NM_001370136.1		c.3307_3312dupGAAGAA	p.Glu1103_Glu1104dup	conservative_inframe_insertion	Exon 16 of 18	NP_001357065.1	Q8WYB5-1
KAT6B	NM_001370137.1		c.3307_3312dupGAAGAA	p.Glu1103_Glu1104dup	conservative_inframe_insertion	Exon 16 of 18	NP_001357066.1	Q8WYB5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KAT6B	ENST00000287239.10	TSL:1 MANE Select	c.3307_3312dupGAAGAA	p.Glu1103_Glu1104dup	conservative_inframe_insertion	Exon 16 of 18	ENSP00000287239.4	Q8WYB5-1
KAT6B	ENST00000372711.2	TSL:1	c.2758_2763dupGAAGAA	p.Glu920_Glu921dup	conservative_inframe_insertion	Exon 16 of 18	ENSP00000361796.1	Q8WYB5-2
KAT6B	ENST00000648725.1		c.3307_3312dupGAAGAA	p.Glu1103_Glu1104dup	conservative_inframe_insertion	Exon 16 of 18	ENSP00000497841.1	Q8WYB5-1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150036

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000126

AC:

AN:

238206

AF XY:

0.00000772

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000286

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000398

AC:

AN:

1455864

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

724470

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32966

American (AMR)

AF:

0.00

AC:

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39604

South Asian (SAS)

AF:

0.0000233

AC:

AN:

85950

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000497

AC:

AN:

1107648

Other (OTH)

AF:

0.00

AC:

AN:

60206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

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:

0.0000133

AC:

AN:

150036

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73172

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40420

American (AMR)

AF:

0.00

AC:

AN:

15056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5098

South Asian (SAS)

AF:

0.00

AC:

AN:

4702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67634

Other (OTH)

AF:

0.00

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

213

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Genitopatellar syndrome (1)

Genitopatellar syndrome;C1863557:Blepharophimosis - intellectual disability syndrome, SBBYS type (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.1

Mutation Taster

=84/16

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over