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
NM_012330.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.89
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
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00239 AC: 363AN: 151898Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00252 AC: 624AN: 247992Hom.: 1 AF XY: 0.00249 AC XY: 335AN XY: 134420
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GnomAD4 exome AF: 0.00281 AC: 4094AN: 1459094Hom.: 8 AF XY: 0.00270 AC XY: 1962AN XY: 725934
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GnomAD4 genome AF: 0.00239 AC: 363AN: 152016Hom.: 0 Cov.: 32 AF XY: 0.00272 AC XY: 202AN XY: 74328
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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
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at