10-74842969-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBS1_SupportingBS2

The NM_012330.4(KAT6B):c.112A>G(p.Thr38Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,094 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 1 hom. )

Consequence

KAT6B
NM_012330.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.34

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PP2

Missense variant where missense usually causes diseases, KAT6B

BP4

Computational evidence support a benign effect (MetaRNN=0.09821576).

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000116 (17/1461890) while in subpopulation SAS AF= 0.000185 (16/86258). AF 95% confidence interval is 0.000115. There are 1 homozygotes in gnomad4_exome. There are 14 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAdExome at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAT6B	NM_012330.4 linkuse as main transcript	c.112A>G	p.Thr38Ala	missense_variant	3/18	ENST00000287239.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAT6B	ENST00000287239.10 linkuse as main transcript	c.112A>G	p.Thr38Ala	missense_variant	3/18	1	NM_012330.4	P2	Q8WYB5-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152204

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251470

Hom.:

AF XY:

0.0000441

AC XY:

AN XY:

135906

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 SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Genitopatellar syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Sep 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Benign

0.81

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.086

FATHMM_MKL

Uncertain

0.85

M_CAP

Benign

0.0069

MetaRNN

Benign

0.098

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

MetaSVM

Benign

-0.96

MutationTaster

Benign

0.99

N;N;N;N;N

PrimateAI

Benign

0.41

Polyphen

0.0, 0.0010

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

Vest4

0.15, 0.14, 0.12, 0.098, 0.099

MutPred

0.16

Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);Loss of phosphorylation at T38 (P = 0.0591);

MVP

0.27

MPC

0.34

ClinPred

0.069

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.062

gMVP

0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over