rs778899637

Variant names:

• chr10-74976264-A-G
• rs778899637
• NM_012330.4:c.1927A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-74976264-A-G
• chr10-74976264-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012330.4(KAT6B):​c.1927A>G​(p.Met643Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M643L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KAT6B NM_012330.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.69
• 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
• RASopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20123419).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT6B	NM_012330.4	MANE Select	c.1927A>G	p.Met643Val	missense	Exon 8 of 18	NP_036462.2
	KAT6B	NM_001370136.1		c.1927A>G	p.Met643Val	missense	Exon 8 of 18	NP_001357065.1
	KAT6B	NM_001370137.1		c.1927A>G	p.Met643Val	missense	Exon 8 of 18	NP_001357066.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT6B	ENST00000287239.10	TSL:1 MANE Select	c.1927A>G	p.Met643Val	missense	Exon 8 of 18	ENSP00000287239.4
	KAT6B	ENST00000372711.2	TSL:1	c.1444+483A>G		intron	N/A	ENSP00000361796.1
	KAT6B	ENST00000648725.1		c.1927A>G	p.Met643Val	missense	Exon 8 of 18	ENSP00000497841.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461838 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Benign	0.89
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.047
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.2	L
PhyloP100		6.7
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.75	N
REVEL	Uncertain	0.35
Sift	Benign	0.039	D
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.60
MutPred		0.17		Loss of catalytic residue at V639 (P = 0.0304)
MVP		0.91
MPC		0.36
ClinPred		0.23	T
GERP RS		4.9
Varity_R		0.22
gMVP		0.19
Mutation Taster		=90/10	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: rs778899637; hg19: chr10-76736022;