chr15-25339133-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
This summary comes from the ClinGen Evidence Repository: The c.*4A>G variant in UBE3A (NM_130838.2) is present in gnomAD v2.1.1 at a frequency of 0.0068% in the European (non-Finnish) sub population (no criteria met). In summary, the c.*4A>G variant in UBE3A is classified as Variant of Uncertain Significance based on the ACMG/AMP criteria (no criteria met). LINK:https://erepo.genome.network/evrepo/ui/classification/CA7435334/MONDO:0007113/032
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000076 ( 0 hom. )
Consequence
UBE3A
NM_130839.5 3_prime_UTR
NM_130839.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.834
Genes affected
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UBE3A | NM_130839.5 | c.*4A>G | 3_prime_UTR_variant | 13/13 | ENST00000648336.2 | ||
SNHG14 | NR_146177.1 | n.18393-52463T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UBE3A | ENST00000648336.2 | c.*4A>G | 3_prime_UTR_variant | 13/13 | NM_130839.5 | P1 | |||
SNHG14 | ENST00000656420.1 | n.5456+60249T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000312 AC: 6AN: 192226Hom.: 0 AF XY: 0.00000958 AC XY: 1AN XY: 104408
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GnomAD4 exome AF: 0.0000761 AC: 106AN: 1393636Hom.: 0 Cov.: 31 AF XY: 0.0000768 AC XY: 53AN XY: 689814
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74340
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2Benign:1
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 23, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 15, 2018 | - - |
Angelman syndrome Uncertain:1
Uncertain significance, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Jun 15, 2023 | The c.*4A>G variant in UBE3A (NM_130838.2) is present in gnomAD v2.1.1 at a frequency of 0.0068% in the European (non-Finnish) sub population (no criteria met). In summary, the c.*4A>G variant in UBE3A is classified as Variant of Uncertain Significance based on the ACMG/AMP criteria (no criteria met). - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at