rs57372986

Positions:

chr10-75025234-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KAT6B. . Gene score misZ 2.8874 (greater than the threshold 3.09). Trascript score misZ 4.8748 (greater than threshold 3.09). GenCC has associacion of gene with RASopathy, genitopatellar syndrome, KAT6B-related multiple congenital anomalies syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type.

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 ClinVar as [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 Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 950 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT6B	NM_012330.4 linkuse as main transcript	c.3649G>T	p.Ala1217Ser	missense_variant	17/18	ENST00000287239.10	NP_036462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT6B	ENST00000287239.10 linkuse as main transcript	c.3649G>T	p.Ala1217Ser	missense_variant	17/18	1	NM_012330.4	ENSP00000287239	P2	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

GnomAD3 exomes

AF:

0.00159

AC:

400

AN:

250962

Hom.:

AF XY:

0.00119

AC XY:

162

AN XY:

135700

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 SAS exome

AF:

0.0000981

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

Gnomad4 AFR exome

AF:

0.0224

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000165

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.00624

AC:

950

AN:

152352

Hom.:

Cov.:

AF XY:

0.00588

AC XY:

438

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0213

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00131

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Dec 27, 2018	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). -

Genitopatellar syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

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;.;.

MutationTaster

Benign

0.84

N;N;N;N;N

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

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