10-74842871-C-G

Position:

• chr10-74842871-C-G

Variant summary

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

The NM_012330.4(KAT6B):​c.14C>G​(p.Ala5Gly) 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: 7.57

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.14C>G	p.Ala5Gly	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.14C>G	p.Ala5Gly	missense_variant	3/18	1	NM_012330.4	ENSP00000287239.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249784 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135578

Gnomad AFR exome AF: 0.0000647

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

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

Feb 23, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	.;T;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.66	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;D;D
MetaSVM	Uncertain	0.38	D
MutationAssessor	Uncertain	2.5	.;M;.;M;M;M;.;.;.;.;.;.;M;.;M;.;M;M;.;.;.;.;.;.;M;.;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.2	.;.;.;.;.;D;.;.;.;.;.;.;.;.;D;.;D;D;.;.;.;.;.;.;D;.;.
REVEL	Uncertain	0.43
Sift	Uncertain	0.0060	.;.;.;.;.;D;.;.;.;.;.;.;.;.;D;.;D;D;.;.;.;.;.;.;D;.;.
Sift4G	Uncertain	0.016	.;.;.;.;.;D;.;.;.;.;.;.;.;.;D;.;D;D;.;.;.;.;.;.;D;.;.
Polyphen		1.0, 1.0	.;D;.;D;D;D;.;.;.;.;.;.;D;.;D;.;D;D;.;.;.;.;.;.;D;.;.
Vest4		0.54, 0.53, 0.59, 0.58, 0.47
MutPred		0.32		Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);Gain of disorder (P = 0.0887);
MVP		0.84
MPC		0.99
ClinPred		0.94	D
GERP RS		6.2
Varity_R		0.51
gMVP		0.65

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

Other links and lift over

dbSNP: rs758465794; hg19: chr10-76602629;