10-75022093-GGAGGAGGAAGAAGAGGAGGAAGAA-GGAGGAGGAAGAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_012330.4(KAT6B):c.3252_3263del(p.Glu1086_Glu1089del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00903 in 1,607,396 control chromosomes in the GnomAD database, including 85 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. E1079E) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0071 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0092 (80 hom.)
• Consequence: KAT6B NM_012330.4 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 5.76

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 10-75022093-GGAGGAGGAAGAA-G is Benign according to our data. Variant chr10-75022093-GGAGGAGGAAGAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 260237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75022093-GGAGGAGGAAGAA-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00705 (1069/151616) while in subpopulation NFE AF= 0.0111 (752/67784). AF 95% confidence interval is 0.0104. There are 5 homozygotes in gnomad4. There are 499 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1068 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAT6B	NM_012330.4	c.3252_3263del	p.Glu1086_Glu1089del	inframe_deletion	16/18	ENST00000287239.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAT6B	ENST00000287239.10	c.3252_3263del	p.Glu1086_Glu1089del	inframe_deletion	16/18	1	NM_012330.4	P2
	ENST00000413431.1	n.65+3005_65+3016del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00705 AC: 1068 AN: 151498 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00214

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00572

Gnomad ASJ AF: 0.00491

Gnomad EAS AF: 0.00927

Gnomad SAS AF: 0.00354

Gnomad FIN AF: 0.00485

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.00687 AC: 1700 AN: 247568 Hom.: 15 AF XY: 0.00704 AC XY: 944 AN XY: 134134

Gnomad AFR exome AF: 0.00213

Gnomad AMR exome AF: 0.00465

Gnomad ASJ exome AF: 0.00481

Gnomad EAS exome AF: 0.0119

Gnomad SAS exome AF: 0.00394

Gnomad FIN exome AF: 0.00470

Gnomad NFE exome AF: 0.00891

Gnomad OTH exome AF: 0.00528

GnomAD4 exome AF: 0.00923 AC: 13443 AN: 1455780 Hom.: 80 AF XY: 0.00923 AC XY: 6686 AN XY: 724302

Gnomad4 AFR exome AF: 0.00191

Gnomad4 AMR exome AF: 0.00479

Gnomad4 ASJ exome AF: 0.00536

Gnomad4 EAS exome AF: 0.0108

Gnomad4 SAS exome AF: 0.00352

Gnomad4 FIN exome AF: 0.00517

Gnomad4 NFE exome AF: 0.0104

Gnomad4 OTH exome AF: 0.00822

GnomAD4 genome AF: 0.00705 AC: 1069 AN: 151616 Hom.: 5 Cov.: 32 AF XY: 0.00673 AC XY: 499 AN XY: 74098

Gnomad4 AFR AF: 0.00215

Gnomad4 AMR AF: 0.00571

Gnomad4 ASJ AF: 0.00491

Gnomad4 EAS AF: 0.00929

Gnomad4 SAS AF: 0.00354

Gnomad4 FIN AF: 0.00485

Gnomad4 NFE AF: 0.0111

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.00500 Hom.: 0

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	KAT6B: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 03, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2020	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 29, 2020	The p.Glu1086_Glu1089del variant in KAT6B is classified as benign because it has been identified in 1.2% (237/19782) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA1. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Genitopatellar syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Intellectual disability Benign:1

Likely benign, no assertion criteria provided

clinical testing

Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille

Jan 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201769534; hg19: chr10-76781851;