Submissions for variant NM_130839.5(UBE3A):c.1269C>T (p.Asp423=)

gnomAD frequency: 0.00117  dbSNP: rs149506027

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel	RCV000144339	SCV002569939	benign	Angelman syndrome	2022-09-01	reviewed by expert panel	curation	The allele frequency of the p.Asp423= variant in UBE3A is 0.18% in European (Non-Finnish) sub population in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). The silent p.Asp423= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP7). In summary, the p.Asp423= variant in UBE3A is classified as benign based on the ACMG/AMP criteria (BA1, BP7).
Eurofins Ntd Llc (ga)	RCV000082342	SCV000114305	benign	not specified	2017-12-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000082342	SCV000169712	benign	not specified	2016-07-15	criteria provided, single submitter	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.
Genetic Services Laboratory, University of Chicago	RCV000082342	SCV000195339	likely benign	not specified	2015-08-10	criteria provided, single submitter	clinical testing
Invitae	RCV000144339	SCV000559144	benign	Angelman syndrome	2024-01-27	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000714144	SCV000844824	benign	not provided	2017-12-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002316275	SCV000850826	likely benign	Inborn genetic diseases	2016-12-21	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000714144	SCV002545220	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	SNHG14: BS2; UBE3A: BP4, BS2
Baylor Genetics	RCV000144339	SCV000188516	uncertain significance	Angelman syndrome	2014-02-14	no assertion criteria provided	clinical testing	possible diagnosis of Angelman syndrome