Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_012330.4(KAT6B):c.130A>T(p.Lys44*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
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]
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 10-74842987-A-T is Pathogenic according to our data. Variant chr10-74842987-A-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1705681.Status of the report is criteria_provided_single_submitter, 1 stars.
Blepharophimosis - intellectual disability syndrome, SBBYS type Pathogenic:1
Sep 01, 2022
3billion
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The variant is not observed in the gnomAD v2.1.1 dataset. Stop-gained (nonsense) is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. -