Variant chr10-74843012-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3

The NM_012330.4(KAT6B):c.155A>C(p.Glu52Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

KAT6B
NM_012330.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.823

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT6B	NM_012330.4 linkuse as main transcript	c.155A>C	p.Glu52Ala	missense_variant	3/18	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.155A>C	p.Glu52Ala	missense_variant	3/18	1	NM_012330.4	ENSP00000287239	P2	Q8WYB5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Oct 13, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.71

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

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.99

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.82

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

0.33

MutationAssessor

Uncertain

2.9

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

MutationTaster

Benign

0.52

D;D;D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-5.2

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

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0020

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

Sift4G

Uncertain

0.0040

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

Polyphen

0.91

P;.;P;P;P;.;.;.;.;.;P;.;P;.;P;P;.;.;.;.;.;.;P;.

Vest4

0.71, 0.69, 0.67, 0.72, 0.68

MutPred

0.39

Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);Loss of disorder (P = 0.1232);

MVP

0.78

MPC

0.68

ClinPred

0.99

GERP RS

6.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.68

gMVP

0.79

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over