rs139928148
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BS1BS2BP4
This summary comes from the ClinGen Evidence Repository: The allele frequency of the p.Asn272Ser variant in UBE3A is 0.013% in European (Non-Finnish) sub population in gnomAD, which is high enough to be classified as likely benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Asn272Ser variant is observed in at least 4 unaffected individuals (internal database) (BS2). Computational analysis prediction tools suggest that the p.Asn272Ser variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Asn272Ser variant in UBE3A is classified as benign based on the ACMG/AMP criteria (BS1, BS2, BP4). LINK:https://erepo.genome.network/evrepo/ui/classification/CA333443/MONDO:0007113/016
Frequency
Consequence
NM_130839.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UBE3A | NM_130839.5 | c.815A>G | p.Asn272Ser | missense_variant | 6/13 | ENST00000648336.2 | |
SNHG14 | NR_146177.1 | n.18393-20237T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UBE3A | ENST00000648336.2 | c.815A>G | p.Asn272Ser | missense_variant | 6/13 | NM_130839.5 | P1 | ||
SNHG14 | ENST00000656420.1 | n.5457-47429T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000103 AC: 26AN: 251344Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135838
GnomAD4 exome AF: 0.0000992 AC: 145AN: 1461786Hom.: 0 Cov.: 32 AF XY: 0.0000935 AC XY: 68AN XY: 727188
GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152322Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74486
ClinVar
Submissions by phenotype
Angelman syndrome Uncertain:3Benign:2
Benign, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Aug 25, 2022 | The allele frequency of the p.Asn272Ser variant in UBE3A is 0.013% in European (Non-Finnish) sub population in gnomAD, which is high enough to be classified as likely benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Asn272Ser variant is observed in at least 4 unaffected individuals (internal database) (BS2). Computational analysis prediction tools suggest that the p.Asn272Ser variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Asn272Ser variant in UBE3A is classified as benign based on the ACMG/AMP criteria (BS1, BS2, BP4). - |
Uncertain significance, no assertion criteria provided | clinical testing | Baylor Genetics | Feb 14, 2014 | possible diagnosis of Angelman syndrome - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 02, 2022 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 07, 2019 | - - |
UBE3A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 22, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at