chr10-75025234-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012330.4(KAT6B):c.3649G>T(p.Ala1217Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,614,156 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 7 hom. )

Consequence

KAT6B
NM_012330.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.45

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003739357).

BP6

Variant 10-75025234-G-T is Benign according to our data. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00624 (950/152352) while in subpopulation AFR AF = 0.0213 (884/41574). AF 95% confidence interval is 0.0201. There are 10 homozygotes in GnomAd4. There are 438 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 950 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT6B	NM_012330.4 link	c.3649G>T	p.Ala1217Ser	missense_variant	Exon 17 of 18	ENST00000287239.10	NP_036462.2	Q8WYB5-1B2RWN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT6B	ENST00000287239.10 link	c.3649G>T	p.Ala1217Ser	missense_variant	Exon 17 of 18	1	NM_012330.4	ENSP00000287239.4		Q8WYB5-1

Frequencies

GnomAD3 genomes

AF:

0.00627

AC:

954

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

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:

0.000162

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00159

AC:

400

AN:

250962

AF XY:

0.00119

show subpopulations

Gnomad AFR exome

AF:

0.0202

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000769

AC:

1124

AN:

1461804

Hom.:

Cov.:

AF XY:

0.000688

AC XY:

500

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.0224

AC:

750

AN:

33474

American (AMR)

AF:

0.00148

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00503

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000165

AC:

183

AN:

1111986

Other (OTH)

AF:

0.00147

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

124

186

248

310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00624

AC:

950

AN:

152352

Hom.:

Cov.:

AF XY:

0.00588

AC XY:

438

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.0213

AC:

884

AN:

41574

American (AMR)

AF:

0.00288

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68038

Other (OTH)

AF:

0.00521

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

148

197

246

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:

0.00254

Hom.:

Bravo

AF:

0.00703

ESP6500AA

AF:

0.0243

AC:

107

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00199

AC:

242

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Dec 27, 2018

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Ala1217Ser in exon 17 of KAT6B: This variant is not expected to have clinical significance because it has been identified in 2.08% (212/10216) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs57372986). -

Mar 03, 2017

GeneDx

Significance: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. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genitopatellar syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.054

T;.;T;.;.;.;.;.;.;T;.;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.95

MetaRNN

Benign

0.0037

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.2

L;.;L;.;.;.;.;.;.;L;.;.

PhyloP100

1.5

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.18

.;.;.;N;.;.;.;.;N;N;.;N

REVEL

Benign

0.17

Sift

Benign

0.43

.;.;.;T;.;.;.;.;T;T;.;T

Sift4G

Benign

0.47

.;.;.;T;.;.;.;.;T;T;.;T

Polyphen

0.0

B;B;B;B;.;.;B;B;B;B;.;B

Vest4

0.14, 0.15, 0.11, 0.13

MVP

0.24

MPC

0.18

ClinPred

0.0025

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.030

gMVP

0.13

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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