Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4BP7
This summary comes from the ClinGen Evidence Repository: The c.282C>T p.Gly94= variant in UBE3A (NM_130838.2) is present in gnomAD v2.1.1 at a frequency of 0.0069% in the European (non-Finnish) sub population (no criteria met). The silent p.Gly94= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP4, BP7). In summary, the c.282C>T p.Gly94= variant in UBE3A is classified as Likely Benign based on the ACMG/AMP criteria (BP4, BP7). LINK:https://erepo.genome.network/evrepo/ui/classification/CA7435667/MONDO:0007113/032
UBE3A (HGNC:12496): (ubiquitin protein ligase E3A) This gene encodes an E3 ubiquitin-protein ligase, part of the ubiquitin protein degradation system. This imprinted gene is maternally expressed in brain and biallelically expressed in other tissues. Maternally inherited deletion of this gene causes Angelman Syndrome, characterized by severe motor and intellectual retardation, ataxia, hypotonia, epilepsy, absence of speech, and characteristic facies. The protein also interacts with the E6 protein of human papillomavirus types 16 and 18, resulting in ubiquitination and proteolysis of tumor protein p53. Alternative splicing of this gene results in three transcript variants encoding three isoforms with different N-termini. Additional transcript variants have been described, but their full length nature has not been determined. [provided by RefSeq, Jul 2008]
SNHG14 (HGNC:37462): (small nucleolar RNA host gene 14) This gene is located within the Prader-Willi critical region and produces a long, spliced paternally-imprinted RNA that initiates within a common upstream promoter region shared by the SNRPN (small nuclear ribonucleoprotein polypeptide N) and SNURF genes. This transcript serves as a host RNA for the small nucleolar RNA, C/D box 115 and 116 clusters. This RNA extends in antisense into the region of the ubiquitin protein ligase E3A gene (UBE3A), and is thought to regulate imprinted expression of UBE3A in the brain. This transcript undergoes extensive alternative splicing, and may initiate and terminate at multiple locations within this genomic region. The full-length structure of all splice forms is not determined. [provided by RefSeq, Mar 2017]
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel
Significance: Likely benign
Review Status: reviewed by expert panel
Collection Method: curation
The c.282C>T p.Gly94= variant in UBE3A (NM_130838.2) is present in gnomAD v2.1.1 at a frequency of 0.0069% in the European (non-Finnish) sub population (no criteria met). The silent p.Gly94= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP4, BP7). In summary, the c.282C>T p.Gly94= variant in UBE3A is classified as Likely Benign based on the ACMG/AMP criteria (BP4, BP7). -
Oct 31, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not provided Benign:1
Mar 03, 2015
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter