rs569172957

Positions:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP3BP6BS2

The NM_012330.4(KAT6B):c.3231_3242delCGAGGAGGAGGA(p.Asp1077_Glu1080del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,611,110 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 8 hom. )

Consequence

KAT6B
NM_012330.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: 7.89

Variant links:

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 links:

ENSG00000234149 (HGNC:):

ENSG00000234149 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PP3

No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

BP6

Variant 10-75022078-GGAGGAGGAGGAC-G is Benign according to our data. Variant chr10-75022078-GGAGGAGGAGGAC-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 260236.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1, Benign=3}. Variant chr10-75022078-GGAGGAGGAGGAC-G is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 363 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT6B	NM_012330.4 link	c.3231_3242delCGAGGAGGAGGA	p.Asp1077_Glu1080del	disruptive_inframe_deletion	16/18	ENST00000287239.10	NP_036462.2	Q8WYB5-1B2RWN8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT6B	ENST00000287239.10 link	c.3231_3242delCGAGGAGGAGGA	p.Asp1077_Glu1080del	disruptive_inframe_deletion	16/18	1	NM_012330.4	ENSP00000287239.4		Q8WYB5-1

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

363

AN:

151898

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000509

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00839

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00335

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00252

AC:

624

AN:

247992

Hom.:

AF XY:

0.00249

AC XY:

335

AN XY:

134420

show subpopulations

Gnomad AFR exome

AF:

0.000570

Gnomad AMR exome

AF:

0.000756

Gnomad ASJ exome

AF:

0.000801

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00825

Gnomad NFE exome

AF:

0.00353

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00281

AC:

4094

AN:

1459094

Hom.:

AF XY:

0.00270

AC XY:

1962

AN XY:

725934

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000784

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00741

Gnomad4 NFE exome

AF:

0.00316

Gnomad4 OTH exome

AF:

0.00211

GnomAD4 genome

AF:

0.00239

AC:

363

AN:

152016

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

202

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.000507

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00839

Gnomad4 NFE

AF:

0.00335

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00222

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 03, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	KAT6B: BS1 -
Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

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

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Aug 01, 2017

KAT6B NM_012330.3 exon16 p.Asp1077_Glu1080del (c.3231_3242delCGAGGAGGAGGA): This variant has not been reported in the literature, but has been identified by our laboratory in 1 individual with a clinical suspicion of a RASopathy. However, this individual also carried a pathogenic variant in a different gene likely to be causative of the phenotype. This variant is not present in large control databases. This variant is present in ClinVar (Variation ID:260236). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant represents an in-frame deletion of 4 amino acids at position 1077 and is not predicted to alter the reading frame. However, the effect of this variant on the protein is unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Genitopatellar syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over