10-74842923-G-C

Variant names:

• chr10-74842923-G-C
• rs748479485
• NM_012330.4:c.66G>C

Variant summary

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

The NM_012330.4(KAT6B):​c.66G>C​(p.Lys22Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KAT6B NM_012330.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.56

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 rank	MANE	Protein	UniProt
KAT6B	NM_012330.4	c.66G>C	p.Lys22Asn	missense_variant	Exon 3 of 18	ENST00000287239.10	NP_036462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT6B	ENST00000287239.10	c.66G>C	p.Lys22Asn	missense_variant	Exon 3 of 18	1	NM_012330.4	ENSP00000287239.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00000796 AC: 2 AN: 251374 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135860

Gnomad AFR exome AF: 0.000123

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 AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727244

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74318

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

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

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Uncertain	0.49	.;T;.;.;T;.;.;.;.;.;.;.;.;.;.;.;T;.;.;.;.;.;.;.;.;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.40	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;D;T
MetaSVM	Uncertain	-0.023	T
MutationAssessor	Benign	1.4	.;L;.;L;L;L;.;.;.;.;.;L;.;L;.;L;L;.;.;.;.;.;.;L;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.5	.;.;.;.;.;D;.;.;.;.;.;.;.;D;.;D;D;.;.;.;.;.;.;D;.;.
REVEL	Uncertain	0.42
Sift	Uncertain	0.016	.;.;.;.;.;D;.;.;.;.;.;.;.;D;.;D;D;.;.;.;.;.;.;D;.;.
Sift4G	Uncertain	0.014	.;.;.;.;.;D;.;.;.;.;.;.;.;D;.;D;D;.;.;.;.;.;.;D;.;.
Polyphen		0.80, 0.87	.;P;.;P;P;P;.;.;.;.;.;P;.;P;.;P;P;.;.;.;.;.;.;P;.;.
Vest4		0.45, 0.44, 0.40, 0.44, 0.44
MutPred		0.34		Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);Loss of methylation at K22 (P = 0.0025);
MVP		0.57
MPC		0.89
ClinPred		0.91	D
GERP RS		3.8
Varity_R		0.61
gMVP		0.55

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: rs748479485; hg19: chr10-76602681;