10-75028886-AGAGGAGGAG-AGAG

Position:

• chr10-75028886-AGAGGAGGAG-AGAG

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.4074_4079delGGAGGA​(p.Glu1359_Glu1360del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00165 in 1,609,654 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (4 hom.)
• Consequence: KAT6B NM_012330.4 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 6.65

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 Benign. Variant got -16 ACMG points.

• BP6: Variant 10-75028886-AGAGGAG-A is Benign according to our data. Variant chr10-75028886-AGAGGAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 260241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75028886-AGAGGAG-A is described in Lovd as [Likely_pathogenic]. Variant chr10-75028886-AGAGGAG-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00135 (203/150850) while in subpopulation NFE AF= 0.00197 (134/67966). AF 95% confidence interval is 0.0017. There are 0 homozygotes in gnomad4. There are 87 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 203 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT6B	NM_012330.4	c.4074_4079delGGAGGA	p.Glu1359_Glu1360del	disruptive_inframe_deletion	18/18	ENST00000287239.10	NP_036462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT6B	ENST00000287239.10	c.4074_4079delGGAGGA	p.Glu1359_Glu1360del	disruptive_inframe_deletion	18/18	1	NM_012330.4	ENSP00000287239.4

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 203 AN: 150732 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000329

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00197

Gnomad OTH AF: 0.000963

GnomAD3 exomes AF: 0.00106 AC: 261 AN: 245752 Hom.: 0 AF XY: 0.00110 AC XY: 146 AN XY: 133306

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.000645

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000551

Gnomad SAS exome AF: 0.0000330

Gnomad FIN exome AF: 0.000143

Gnomad NFE exome AF: 0.00186

Gnomad OTH exome AF: 0.000990

GnomAD4 exome AF: 0.00168 AC: 2446 AN: 1458804 Hom.: 4 AF XY: 0.00157 AC XY: 1142 AN XY: 725894

Gnomad4 AFR exome AF: 0.00146

Gnomad4 AMR exome AF: 0.000606

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000813

Gnomad4 FIN exome AF: 0.000169

Gnomad4 NFE exome AF: 0.00203

Gnomad4 OTH exome AF: 0.00156

GnomAD4 genome AF: 0.00135 AC: 203 AN: 150850 Hom.: 0 Cov.: 32 AF XY: 0.00118 AC XY: 87 AN XY: 73772

Gnomad4 AFR AF: 0.00151

Gnomad4 AMR AF: 0.000328

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00197

Gnomad4 OTH AF: 0.000953

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Genitopatellar syndrome Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2017	This variant is associated with the following publications: (PMID: 28857140, 26370006, 26334766, 25424711) -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	KAT6B: PS2:Moderate, BS1, BS2 -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Genitopatellar syndrome;C1863557:Blepharophimosis - intellectual disability syndrome, SBBYS type Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 04, 2022

- -

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: rs367634881; hg19: chr10-76788644;