10-75029102-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012330.4(KAT6B):c.4278C>T(p.Ala1426Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 1,614,018 control chromosomes in the GnomAD database, including 685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 141 hom., cov: 32)

Exomes 𝑓: 0.016 ( 544 hom. )

Consequence

KAT6B
NM_012330.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.03

Publications

6 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 10-75029102-C-T is Benign according to our data. Variant chr10-75029102-C-T is described in ClinVar as Benign. ClinVar VariationId is 260245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.076 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT6B	NM_012330.4 link	c.4278C>T	p.Ala1426Ala	synonymous_variant	Exon 18 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.4278C>T	p.Ala1426Ala	synonymous_variant	Exon 18 of 18	1	NM_012330.4	ENSP00000287239.4		Q8WYB5-1

Frequencies

GnomAD3 genomes

AF:

0.0325

AC:

4936

AN:

152018

Hom.:

141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0577

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0448

Gnomad ASJ

AF:

0.0219

Gnomad EAS

AF:

0.0824

Gnomad SAS

AF:

0.0286

Gnomad FIN

AF:

0.0335

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.0335

GnomAD2 exomes

AF:

0.0349

AC:

8780

AN:

251296

AF XY:

0.0317

show subpopulations

Gnomad AFR exome

AF:

0.0568

Gnomad AMR exome

AF:

0.0853

Gnomad ASJ exome

AF:

0.0216

Gnomad EAS exome

AF:

0.0854

Gnomad FIN exome

AF:

0.0324

Gnomad NFE exome

AF:

0.0118

Gnomad OTH exome

AF:

0.0339

GnomAD4 exome

AF:

0.0163

AC:

23832

AN:

1461882

Hom.:

544

Cov.:

AF XY:

0.0163

AC XY:

11865

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0635

AC:

2127

AN:

33480

American (AMR)

AF:

0.0781

AC:

3491

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0235

AC:

613

AN:

26136

East Asian (EAS)

AF:

0.0679

AC:

2697

AN:

39700

South Asian (SAS)

AF:

0.0263

AC:

2266

AN:

86254

European-Finnish (FIN)

AF:

0.0316

AC:

1689

AN:

53418

Middle Eastern (MID)

AF:

0.0602

AC:

347

AN:

5768

European-Non Finnish (NFE)

AF:

0.00826

AC:

9183

AN:

1112010

Other (OTH)

AF:

0.0235

AC:

1419

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

1560

3119

4679

6238

7798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.0325

AC:

4938

AN:

152136

Hom.:

141

Cov.:

AF XY:

0.0338

AC XY:

2512

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0577

AC:

2395

AN:

41476

American (AMR)

AF:

0.0446

AC:

683

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0219

AC:

AN:

3466

East Asian (EAS)

AF:

0.0824

AC:

427

AN:

5182

South Asian (SAS)

AF:

0.0285

AC:

137

AN:

4814

European-Finnish (FIN)

AF:

0.0335

AC:

354

AN:

10582

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0114

AC:

774

AN:

67996

Other (OTH)

AF:

0.0327

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

231

461

692

922

1153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0216

Hom.:

132

Bravo

AF:

0.0366

Asia WGS

AF:

0.0580

AC:

201

AN:

3478

EpiCase

AF:

0.0141

EpiControl

AF:

0.0147

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 11, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 05, 2016

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.020

(source)

DANN

Benign

0.75

PhyloP100

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

polymorphism (auto)

(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