rs139082033
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
This summary comes from the ClinGen Evidence Repository: The allele frequency of the c.1707C>T p.(Tyr569=) variant in UBE3A (NM_130838.2) is 0.15% in the 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). In summary, the c.1707C>T p.(Tyr569=) variant in UBE3A is classified as Benign based on the ACMG/AMP criteria (BA1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA205044/MONDO:0007113/016
Frequency
Consequence
NM_130839.5 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UBE3A | NM_130839.5 | c.1767C>T | p.Tyr589= | synonymous_variant | 8/13 | ENST00000648336.2 | |
SNHG14 | NR_146177.1 | n.18393-34713G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UBE3A | ENST00000648336.2 | c.1767C>T | p.Tyr589= | synonymous_variant | 8/13 | NM_130839.5 | P1 | ||
SNHG14 | ENST00000656420.1 | n.5457-61905G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000927 AC: 141AN: 152070Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000781 AC: 196AN: 251006Hom.: 0 AF XY: 0.000825 AC XY: 112AN XY: 135790
GnomAD4 exome AF: 0.00165 AC: 2404AN: 1460800Hom.: 6 Cov.: 30 AF XY: 0.00158 AC XY: 1148AN XY: 726742
GnomAD4 genome ? AF: 0.000920 AC: 140AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.000766 AC XY: 57AN XY: 74414
ClinVar
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 05, 2017 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 10, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 12, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 15, 2016 | 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. - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Angelman syndrome Uncertain:1Benign:2
Uncertain significance, no assertion criteria provided | clinical testing | Baylor Genetics | Feb 14, 2014 | possible diagnosis of Angelman syndrome - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Jun 30, 2022 | The allele frequency of the c.1707C>T p.(Tyr569=) variant in UBE3A (NM_130838.2) is 0.15% in the 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). In summary, the c.1707C>T p.(Tyr569=) variant in UBE3A is classified as Benign based on the ACMG/AMP criteria (BA1). - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | UBE3A: BP4, BP7, BS1 - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 25, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at