10-74842934-G-A

Position:

• chr10-74842934-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012330.4(KAT6B):​c.77G>A​(p.Arg26Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KAT6B NM_012330.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT6B	NM_012330.4	c.77G>A	p.Arg26Lys	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	c.77G>A	p.Arg26Lys	missense_variant	3/18	1	NM_012330.4	ENSP00000287239.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Genitopatellar syndrome;C1863557:Blepharophimosis - intellectual disability syndrome, SBBYS type Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Mar 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.70	.;D;.;.;D;.;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;.
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.98
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.74	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	0.77	D
MutationAssessor	Uncertain	2.6	.;M;.;M;M;M;.;.;.;.;.;M;.;M;.;M;M;.;.;.;.;.;.;M;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-2.7	.;.;.;.;.;D;.;.;.;.;.;.;.;D;.;D;D;.;.;.;.;.;.;D;.
REVEL	Uncertain	0.62
Sift	Uncertain	0.0030	.;.;.;.;.;D;.;.;.;.;.;.;.;D;.;D;D;.;.;.;.;.;.;D;.
Sift4G	Uncertain	0.0070	.;.;.;.;.;D;.;.;.;.;.;.;.;D;.;D;D;.;.;.;.;.;.;D;.
Polyphen		0.99, 1.0	.;D;.;D;D;D;.;.;.;.;.;D;.;D;.;D;D;.;.;.;.;.;.;D;.
Vest4		0.68, 0.68, 0.74, 0.71
MutPred		0.36		Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);Gain of methylation at R26 (P = 0.0076);
MVP		0.92
MPC		1.1
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.49
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr10-76602692;