NM_012330.4:c.3310_3312dupGAA

Variant names:

• chr10-75022147-G-GGAA
• rs71929101
• NM_012330.4:c.3310_3312dupGAA

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_012330.4(KAT6B):​c.3310_3312dupGAA​(p.Glu1104dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00636 in 1,605,902 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (2 hom., cov: 22)
  • Exomes 𝑓: 0.0065 (19 hom.)
• Consequence: KAT6B NM_012330.4 conservative_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 3.08

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]

ENSG00000234149 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 10-75022147-G-GGAA is Benign according to our data. Variant chr10-75022147-G-GGAA is described in ClinVar as [Likely_benign]. Clinvar id is 260238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 801 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT6B	NM_012330.4	c.3310_3312dupGAA	p.Glu1104dup	conservative_inframe_insertion	Exon 16 of 18	ENST00000287239.10	NP_036462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT6B	ENST00000287239.10	c.3310_3312dupGAA	p.Glu1104dup	conservative_inframe_insertion	Exon 16 of 18	1	NM_012330.4	ENSP00000287239.4

Frequencies

GnomAD3 genomes AF: 0.00535 AC: 803 AN: 150036 Hom.: 2 Cov.: 22

Gnomad AFR AF: 0.00146

Gnomad AMI AF: 0.0881

Gnomad AMR AF: 0.00697

Gnomad ASJ AF: 0.00549

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00191

Gnomad FIN AF: 0.00250

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.00727

Gnomad OTH AF: 0.00389

GnomAD3 exomes AF: 0.00505 AC: 1203 AN: 238206 Hom.: 2 AF XY: 0.00512 AC XY: 664 AN XY: 129600

Gnomad AFR exome AF: 0.000946

Gnomad AMR exome AF: 0.00453

Gnomad ASJ exome AF: 0.00358

Gnomad EAS exome AF: 0.000168

Gnomad SAS exome AF: 0.00201

Gnomad FIN exome AF: 0.00298

Gnomad NFE exome AF: 0.00807

Gnomad OTH exome AF: 0.00455

GnomAD4 exome AF: 0.00646 AC: 9410 AN: 1455750 Hom.: 19 Cov.: 31 AF XY: 0.00649 AC XY: 4704 AN XY: 724420

Gnomad4 AFR exome AF: 0.000819

Gnomad4 AMR exome AF: 0.00426

Gnomad4 ASJ exome AF: 0.00372

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.00159

Gnomad4 FIN exome AF: 0.00328

Gnomad4 NFE exome AF: 0.00760

Gnomad4 OTH exome AF: 0.00565

GnomAD4 genome AF: 0.00533 AC: 801 AN: 150152 Hom.: 2 Cov.: 22 AF XY: 0.00517 AC XY: 379 AN XY: 73298

Gnomad4 AFR AF: 0.00146

Gnomad4 AMR AF: 0.00696

Gnomad4 ASJ AF: 0.00549

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.00192

Gnomad4 FIN AF: 0.00250

Gnomad4 NFE AF: 0.00728

Gnomad4 OTH AF: 0.00385

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

KAT6B: BS2 -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 21, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified Benign:3

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 28, 2017

Institute for Genomic Medicine (IGM) Clinical Laboratory, Nationwide Children's Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

BS1, BS2, BP3; This alteration has an allele frequency that is greater than expected for the associated disease, was seen in a healthy adult where full penetrance of the disorder is expected at an early age, and is an in-frame deletion/insertion in a repetitive region without a known function. -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genitopatellar syndrome Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: rs71929101; hg19: chr10-76781905;