10-75030558-A-G

Variant names:

• chr10-75030558-A-G
• rs199470485
• NM_012330.4:c.5734A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_012330.4(KAT6B):​c.5734A>G​(p.Arg1912Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KAT6B NM_012330.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.38
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• blepharophimosis - intellectual disability syndrome, SBBYS type

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• genitopatellar syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• KAT6B-related multiple congenital anomalies syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• RASopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.821

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012330.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT6B	NM_012330.4	MANE Select	c.5734A>G	p.Arg1912Gly	missense	Exon 18 of 18	NP_036462.2	Q8WYB5-1
	KAT6B	NM_001370136.1		c.5734A>G	p.Arg1912Gly	missense	Exon 18 of 18	NP_001357065.1	Q8WYB5-1
	KAT6B	NM_001370137.1		c.5734A>G	p.Arg1912Gly	missense	Exon 18 of 18	NP_001357066.1	Q8WYB5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT6B	ENST00000287239.10	TSL:1 MANE Select	c.5734A>G	p.Arg1912Gly	missense	Exon 18 of 18	ENSP00000287239.4	Q8WYB5-1
	KAT6B	ENST00000372711.2	TSL:1	c.5185A>G	p.Arg1729Gly	missense	Exon 18 of 18	ENSP00000361796.1	Q8WYB5-2
	KAT6B	ENST00000648725.1		c.5734A>G	p.Arg1912Gly	missense	Exon 18 of 18	ENSP00000497841.1	Q8WYB5-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456166 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 723170

African (AFR) AF: 0.00 AC: 0 AN: 33286

American (AMR) AF: 0.00 AC: 0 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26006

East Asian (EAS) AF: 0.00 AC: 0 AN: 39548

South Asian (SAS) AF: 0.00 AC: 0 AN: 86138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107458

Other (OTH) AF: 0.00 AC: 0 AN: 60084

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.89	D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.010	D
Polyphen		0.99	D
Vest4		0.76
MutPred		0.30		Loss of MoRF binding (P = 0.0066)
MVP		0.88
MPC		0.86
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.56
gMVP		0.69
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

dbSNP: rs199470485; hg19: chr10-76790316;