rs10824245

Variant names:

• chr10-74907041-C-T
• rs10824245
• NM_012330.4:c.622-52929C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012330.4(KAT6B):​c.622-52929C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,142 control chromosomes in the GnomAD database, including 13,148 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (13148 hom., cov: 32)
• Consequence: KAT6B NM_012330.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

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.622-52929C>T		intron	N/A	NP_036462.2
	KAT6B	NM_001370136.1		c.622-52929C>T		intron	N/A	NP_001357065.1
	KAT6B	NM_001370137.1		c.622-52929C>T		intron	N/A	NP_001357066.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAT6B	ENST00000287239.10	TSL:1 MANE Select	c.622-52929C>T		intron	N/A	ENSP00000287239.4
	KAT6B	ENST00000372711.2	TSL:1	c.622-52929C>T		intron	N/A	ENSP00000361796.1
	KAT6B	ENST00000648725.1		c.622-52929C>T		intron	N/A	ENSP00000497841.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 47032 AN: 152024 Hom.: 13099 Cov.: 32

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.268

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.310 AC: 47133 AN: 152142 Hom.: 13148 Cov.: 32 AF XY: 0.306 AC XY: 22752 AN XY: 74398

African (AFR) AF: 0.735 AC: 30464 AN: 41474

American (AMR) AF: 0.229 AC: 3498 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3468

East Asian (EAS) AF: 0.362 AC: 1873 AN: 5170

South Asian (SAS) AF: 0.423 AC: 2041 AN: 4824

European-Finnish (FIN) AF: 0.0520 AC: 551 AN: 10606

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7518 AN: 67994

Other (OTH) AF: 0.268 AC: 567 AN: 2116

Alfa AF: 0.174 Hom.: 2299

Bravo AF: 0.335

Asia WGS AF: 0.395 AC: 1375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.67
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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: rs10824245; hg19: chr10-76666799;