ClinVar Genomic variation as it relates to human health
NM_130839.5(UBE3A):c.1472_1476del (p.Leu490_Tyr491insTer)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_130839.5(UBE3A):c.1472_1476del (p.Leu490_Tyr491insTer)
Variation ID: 217362 Accession: VCV000217362.10
- Type and length
-
Microsatellite, 5 bp
- Location
-
Cytogenetic: 15q11.2 15: 25370698-25370702 (GRCh38) [ NCBI UCSC ] 15: 25615845-25615849 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 26, 2015 Feb 14, 2024 Mar 10, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_130839.5:c.1472_1476del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_570854.1:p.Leu490_Tyr491insTer nonsense NM_000462.3:c.1481_1485delATTAT NM_000462.5:c.1481_1485del NP_000453.2:p.Leu493_Tyr494insTer nonsense NM_001354505.1:c.1472_1476del NP_001341434.1:p.Leu490_Tyr491insTer nonsense NM_001354506.2:c.1412_1416del NP_001341435.1:p.Leu470_Tyr471insTer nonsense NM_001354507.2:c.1412_1416del NP_001341436.1:p.Leu470_Tyr471insTer nonsense NM_001354508.2:c.1412_1416del NP_001341437.1:p.Leu470_Tyr471insTer nonsense NM_001354509.2:c.1412_1416del NP_001341438.1:p.Leu470_Tyr471insTer nonsense NM_001354511.2:c.1412_1416del NP_001341440.1:p.Leu470_Tyr471insTer nonsense NM_001354512.2:c.1412_1416del NP_001341441.1:p.Leu470_Tyr471insTer nonsense NM_001354513.2:c.1412_1416del NP_001341442.1:p.Leu470_Tyr471insTer nonsense NM_001354523.2:c.1412_1416del NP_001341452.1:p.Leu470_Tyr471insTer nonsense NM_001354526.1:c.1412_1416del NP_001341455.1:p.Leu470_Tyr471insTer nonsense NM_001354538.2:c.1472_1476del NP_001341467.1:p.Leu490_Tyr491insTer nonsense NM_001354539.2:c.1412_1416del NP_001341468.1:p.Leu470_Tyr471insTer nonsense NM_001354540.2:c.1412_1416del NP_001341469.1:p.Leu470_Tyr471insTer nonsense NM_001354541.2:c.1412_1416del NP_001341470.1:p.Leu470_Tyr471insTer nonsense NM_001354542.2:c.1412_1416del NP_001341471.1:p.Leu470_Tyr471insTer nonsense NM_001354543.2:c.1412_1416del NP_001341472.1:p.Leu470_Tyr471insTer nonsense NM_001354544.2:c.1412_1416del NP_001341473.1:p.Leu470_Tyr471insTer nonsense NM_001354545.2:c.1472_1476del NP_001341474.1:p.Leu490_Tyr491insTer nonsense NM_001354546.2:c.1295_1299del NP_001341475.1:p.Leu431_Tyr432insTer nonsense NM_001354547.2:c.1412_1416del NP_001341476.1:p.Leu470_Tyr471insTer nonsense NM_001354548.2:c.1412_1416del NP_001341477.1:p.Leu470_Tyr471insTer nonsense NM_001354549.2:c.1412_1416del NP_001341478.1:p.Leu470_Tyr471insTer nonsense NM_001354550.2:c.361+4763_361+4767del intron variant NM_001354551.2:c.301+4763_301+4767del intron variant NM_001374461.1:c.1412_1416del NP_001361390.1:p.Leu470_Tyr471insTer nonsense NM_130838.1:c.1412_1416del NM_130838.4:c.1412_1416del NP_570853.1:p.Leu470_Tyr471insTer nonsense NR_148916.2:n.1983ATTAT[1] non-coding transcript variant NC_000015.10:g.25370698ATAAT[1] NC_000015.9:g.25615845ATAAT[1] NG_009268.1:g.73275ATTAT[1] LRG_15:g.73275ATTAT[1] LRG_15t1:c.1412_1416del - Protein change
- Other names
- -
- Canonical SPDI
- NC_000015.10:25370697:ATAATATAAT:ATAAT
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
UBE3A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
36 | 1213 | |
SNHG14 | - | - | GRCh38 | 4 | 1113 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (2) |
criteria provided, single submitter
|
Mar 10, 2023 | RCV000201275.2 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Jul 18, 2021 | RCV000633514.10 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jan 2, 2020 | RCV001799632.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Pathogenic
(Jul 18, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Angelman syndrome
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000754751.5
First in ClinVar: May 28, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Tyr471*) in the UBE3A gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Tyr471*) in the UBE3A gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in UBE3A are known to be pathogenic (PMID: 25212744). This variant has been reported in 2 siblings and an unrelated individual affected with Angelman syndrome (PMID: 14981718, 19213023). This variant has also been reported as c.1993del5 and c.1407_1411del5 in the literature. ClinVar contains an entry for this variant (Variation ID: 217362). This variant is not present in population databases (ExAC no frequency). (less)
|
|
Pathogenic
(Jan 01, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Angelman syndrome
Affected status: yes
Allele origin:
de novo
|
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV000965727.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
|
|
Pathogenic
(Jan 02, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Epileptic encephalopathy
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
|
Génétique des Maladies du Développement, Hospices Civils de Lyon
Accession: SCV002043735.1
First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022 |
Sex: female
Comment on evidence:
truncating variant. Fits with phenotype
|
|
Pathogenic
(Mar 10, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV003840634.1
First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25212744, 27174604, 36011358, 31440721, 14981718) (less)
|
|
Pathogenic
(Mar 06, 2015)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000256051.1
First in ClinVar: Oct 26, 2015 Last updated: Oct 26, 2015 |
|
|
Pathogenic
(Jan 01, 2019)
|
no assertion criteria provided
Method: clinical testing
|
Angelman syndrome
Affected status: yes
Allele origin:
de novo
|
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille
Accession: SCV001428381.1
First in ClinVar: Aug 17, 2020 Last updated: Aug 17, 2020 |
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. | Richards S | Genetics in medicine : official journal of the American College of Medical Genetics | 2015 | PMID: 25741868 |
Mutation Update for UBE3A variants in Angelman syndrome. | Sadikovic B | Human mutation | 2014 | PMID: 25212744 |
Novel UBE3A mutations causing Angelman syndrome: different parental origin for single nucleotide changes and multiple nucleotide deletions or insertions. | Camprubí C | American journal of medical genetics. Part A | 2009 | PMID: 19213023 |
Investigation of UBE3A and MECP2 in Angelman syndrome (AS) and patients with features of AS. | Hitchins MP | American journal of medical genetics. Part A | 2004 | PMID: 14981718 |
Text-mined citations for rs863225068 ...
HelpRecord last updated Jun 23, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.