10-75028886-AGAGGAGGAG-AGAGGAG

Position:

chr10-75028886-AGAGGAGGAG-AGAGGAG

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_012330.4(KAT6B):c.4077_4079del(p.Glu1368del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000214 in 1,608,366 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

KAT6B
NM_012330.4 inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 4.23

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 10-75028886-AGAG-A is Benign according to our data. Variant chr10-75028886-AGAG-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 561618.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000351 (53/150846) while in subpopulation AFR AF= 0.000968 (39/40270). AF 95% confidence interval is 0.000728. There are 0 homozygotes in gnomad4. There are 30 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 53 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT6B	NM_012330.4 linkuse as main transcript	c.4077_4079del	p.Glu1368del	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 linkuse as main transcript	c.4077_4079del	p.Glu1368del	inframe_deletion	18/18	1	NM_012330.4	ENSP00000287239	P2	Q8WYB5-1

Frequencies

GnomAD3 genomes

AF:

0.000352

AC:

AN:

150728

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000971

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000236

AC:

AN:

245752

Hom.:

AF XY:

0.000240

AC XY:

AN XY:

133306

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.000323

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.0000551

Gnomad SAS exome

AF:

0.0000989

Gnomad FIN exome

AF:

0.0000956

Gnomad NFE exome

AF:

0.000171

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000200

AC:

291

AN:

1457520

Hom.:

AF XY:

0.000190

AC XY:

138

AN XY:

725270

show subpopulations

Gnomad4 AFR exome

AF:

0.00127

Gnomad4 AMR exome

AF:

0.000426

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.0000563

Gnomad4 NFE exome

AF:

0.000164

Gnomad4 OTH exome

AF:

0.000266

GnomAD4 genome

AF:

0.000351

AC:

AN:

150846

Hom.:

Cov.:

AF XY:

0.000407

AC XY:

AN XY:

73770

show subpopulations

Gnomad4 AFR

AF:

0.000968

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000431

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

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

Mar 30, 2021

KAT6B NM_012330.3 exon 18 p.Glu1368del (c.4077_4079del): This variant has not been reported in the literature but is present in 3/30724 South Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs772530975). This variant is present in ClinVar (Variation ID:260242). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant represents an in-frame deletion of 1 Glutamic acid (Glu) within a larger repeat region of several Glutamic acid residues 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. -

Genitopatellar syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 21, 2024

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 23, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2020

- -

KAT6B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 23, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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