rs569172957

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]

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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
KAT6BNM_012330.4 linkc.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
KAT6BENST00000287239.10 linkc.3231_3242delCGAGGAGGAGGA p.Asp1077_Glu1080del disruptive_inframe_deletion 16/181 NM_012330.4 ENSP00000287239.4 Q8WYB5-1

Frequencies

GnomAD3 genomes
AF:
0.00239
AC:
363
AN:
151898
Hom.:
0
Cov.:
32
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.:
1
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.:
8
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.:
0
Cov.:
32
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.:
0

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 submitterclinical testingGeneDxJun 03, 2020- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenSep 01, 2024KAT6B: BS1 -
Likely benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Likely benign, no assertion criteria providedclinical testingLaboratory 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 submitterclinical testingCenter for Genomics, Ann and Robert H. Lurie Children's Hospital of ChicagoAug 01, 2017KAT6B 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 submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Genitopatellar syndrome Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 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.

Other links and lift over

dbSNP: rs569172957; hg19: chr10-76781836; API