10-75022093-GGAGGAGGAAGAAGAGGAGGAAGAA-GGAGGAGGAAGAAGAGGAGGAAGAAGAGGAGGAAGAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_012330.4(KAT6B):c.3252_3263dup(p.Glu1086_Glu1089dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.0000722 in 1,607,312 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: KAT6B NM_012330.4 inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 10-75022093-G-GGAGGAGGAAGAA is Benign according to our data. Variant chr10-75022093-G-GGAGGAGGAAGAA is described in ClinVar as [Likely_benign]. Clinvar id is 1663325.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000376 (57/151502) while in subpopulation AFR AF= 0.00121 (50/41212). AF 95% confidence interval is 0.000945. There are 0 homozygotes in gnomad4. There are 31 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 57 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAT6B	NM_012330.4	c.3252_3263dup	p.Glu1086_Glu1089dup	inframe_insertion	16/18	ENST00000287239.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAT6B	ENST00000287239.10	c.3252_3263dup	p.Glu1086_Glu1089dup	inframe_insertion	16/18	1	NM_012330.4	P2
	ENST00000413431.1	n.65+3016_65+3017insTTCTTCCTCCTC		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.000376 AC: 57 AN: 151502 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00121

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000101 AC: 25 AN: 247568 Hom.: 0 AF XY: 0.0000820 AC XY: 11 AN XY: 134134

Gnomad AFR exome AF: 0.00113

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000901

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000405 AC: 59 AN: 1455810 Hom.: 0 Cov.: 33 AF XY: 0.0000400 AC XY: 29 AN XY: 724312

Gnomad4 AFR exome AF: 0.000927

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.000116

GnomAD4 genome AF: 0.000376 AC: 57 AN: 151502 Hom.: 0 Cov.: 32 AF XY: 0.000419 AC XY: 31 AN XY: 73972

Gnomad4 AFR AF: 0.00121

Gnomad4 AMR AF: 0.000329

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.000479

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Genitopatellar syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

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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;