Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_012330.4(KAT6B):c.3649G>T(p.Ala1217Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,614,156 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
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 Gene-Disease associations (from GenCC):
blepharophimosis - intellectual disability syndrome, SBBYS type
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.003739357).
BP6
Variant 10-75025234-G-T is Benign according to our data. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-75025234-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 260239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00624 (950/152352) while in subpopulation AFR AF = 0.0213 (884/41574). AF 95% confidence interval is 0.0201. There are 10 homozygotes in GnomAd4. There are 438 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
p.Ala1217Ser in exon 17 of KAT6B: This variant is not expected to have clinical significance because it has been identified in 2.08% (212/10216) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs57372986). -
Mar 03, 2017
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -