10-74842961-C-T

Position:

chr10-74842961-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP6_ModerateBS1BS2

The NM_012330.4(KAT6B):c.104C>T(p.Ala35Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

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

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

KAT6B
NM_012330.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.57

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 -9 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.

BP6

Variant 10-74842961-C-T is Benign according to our data. Variant chr10-74842961-C-T is described in ClinVar as [Benign]. Clinvar id is 2051769.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000301 (44/1461868) while in subpopulation MID AF= 0.000173 (1/5768). AF 95% confidence interval is 0.0000245. There are 0 homozygotes in gnomad4_exome. There are 18 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAT6B	NM_012330.4 linkuse as main transcript	c.104C>T	p.Ala35Val	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.104C>T	p.Ala35Val	missense_variant	3/18	1	NM_012330.4	P2	Q8WYB5-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251454

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Genitopatellar syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 03, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

.;D;.;.;D;.;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;.

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.99

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.61

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

0.24

MutationAssessor

Uncertain

2.1

.;M;.;M;M;M;.;.;.;.;.;M;.;M;.;M;M;.;.;.;.;.;.;M;.

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.2

.;.;.;.;.;D;.;.;.;.;.;.;.;D;.;D;D;.;.;.;.;.;.;D;.

REVEL

Uncertain

0.54

Sift

Benign

0.054

.;.;.;.;.;T;.;.;.;.;.;.;.;T;.;T;D;.;.;.;.;.;.;D;.

Sift4G

Benign

0.12

.;.;.;.;.;T;.;.;.;.;.;.;.;T;.;T;D;.;.;.;.;.;.;T;.

Polyphen

1.0

.;D;.;D;D;D;.;.;.;.;.;D;.;D;.;D;D;.;.;.;.;.;.;D;.

Vest4

0.84, 0.82, 0.74, 0.85, 0.91

MutPred

0.25

Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);Loss of disorder (P = 0.0921);

MVP

0.85

MPC

1.0

ClinPred

0.84

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.74

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