ClinVar Genomic variation as it relates to human health
NM_130839.5(UBE3A):c.2540C>T (p.Pro847Leu)
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
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NM_130839.5(UBE3A):c.2540C>T (p.Pro847Leu)
Variation ID: 155992 Accession: VCV000155992.10
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 15q11.2 15: 25339216 (GRCh38) [ NCBI UCSC ] 15: 25584363 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 4, 2014 May 1, 2024 Jul 26, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_130839.5:c.2540C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_570854.1:p.Pro847Leu missense NM_000462.3:c.2549C>T NM_000462.5:c.2549C>T NP_000453.2:p.Pro850Leu missense NM_001354505.1:c.2540C>T NP_001341434.1:p.Pro847Leu missense NM_001354506.2:c.2480C>T NP_001341435.1:p.Pro827Leu missense NM_001354507.2:c.2480C>T NP_001341436.1:p.Pro827Leu missense NM_001354508.2:c.2480C>T NP_001341437.1:p.Pro827Leu missense NM_001354509.2:c.2480C>T NP_001341438.1:p.Pro827Leu missense NM_001354511.2:c.2480C>T NP_001341440.1:p.Pro827Leu missense NM_001354512.2:c.2480C>T NP_001341441.1:p.Pro827Leu missense NM_001354513.2:c.2480C>T NP_001341442.1:p.Pro827Leu missense NM_001354523.2:c.2480C>T NP_001341452.1:p.Pro827Leu missense NM_001354526.1:c.2480C>T NP_001341455.1:p.Pro827Leu missense NM_001354538.2:c.2540C>T NP_001341467.1:p.Pro847Leu missense NM_001354539.2:c.2480C>T NP_001341468.1:p.Pro827Leu missense NM_001354540.2:c.2480C>T NP_001341469.1:p.Pro827Leu missense NM_001354541.2:c.2480C>T NP_001341470.1:p.Pro827Leu missense NM_001354542.2:c.2480C>T NP_001341471.1:p.Pro827Leu missense NM_001354543.2:c.2480C>T NP_001341472.1:p.Pro827Leu missense NM_001354544.2:c.2480C>T NP_001341473.1:p.Pro827Leu missense NM_001354545.2:c.2384C>T NP_001341474.1:p.Pro795Leu missense NM_001354546.2:c.2363C>T NP_001341475.1:p.Pro788Leu missense NM_001354547.2:c.2324C>T NP_001341476.1:p.Pro775Leu missense NM_001354548.2:c.2324C>T NP_001341477.1:p.Pro775Leu missense NM_001354549.2:c.2315C>T NP_001341478.1:p.Pro772Leu missense NM_001354550.2:c.1289C>T NP_001341479.1:p.Pro430Leu missense NM_001354551.2:c.1229C>T NP_001341480.1:p.Pro410Leu missense NM_001374461.1:c.2480C>T NP_001361390.1:p.Pro827Leu missense NM_130838.4:c.2480C>T NP_570853.1:p.Pro827Leu missense NR_148916.2:n.3052C>T non-coding transcript variant NC_000015.10:g.25339216G>A NC_000015.9:g.25584363G>A NG_009268.1:g.104766C>T LRG_15:g.104766C>T LRG_15t1:c.2480C>T - Protein change
- P827L, P430L, P772L, P410L, P847L, P850L, P775L, P788L, P795L
- Other names
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- Canonical SPDI
- NC_000015.10:25339215:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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. |
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UBE3A | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
34 | 1202 | |
SNHG14 | - | - | GRCh38 | 4 | 1102 |
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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Sep 5, 2022 | RCV000144315.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 26, 2023 | RCV003389042.1 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Sep 29, 2021 | RCV002514772.2 |
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
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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. |
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Pathogenic
(Jul 26, 2023)
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criteria provided, single submitter
Method: clinical testing
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Neurodevelopmental disorder
Affected status: yes
Allele origin:
germline
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Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes
Accession: SCV004101149.1
First in ClinVar: Nov 11, 2023 Last updated: Nov 11, 2023 |
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Likely pathogenic
(Sep 05, 2022)
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criteria provided, single submitter
Method: clinical testing
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Angelman syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000964232.4
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has … (more)
In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 155992). This variant is also known as c.2540C>T. This missense change has been observed in individuals with clinical features of Angelman syndrome and Angelman syndome (PMID: 25212744, 29188609). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 827 of the UBE3A protein (p.Pro827Leu). (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Angelman syndrome
Affected status: yes
Allele origin:
de novo
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Molecular Genetics Lab, CHRU Brest
Accession: SCV004697584.1
First in ClinVar: Mar 05, 2024 Last updated: Mar 05, 2024 |
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Likely pathogenic
(Sep 29, 2021)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV003572172.2
First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024 |
Comment:
The c.2480C>T (p.P827L) alteration is located in exon 10 (coding exon 10) of the UBE3A gene. This alteration results from a C to T substitution … (more)
The c.2480C>T (p.P827L) alteration is located in exon 10 (coding exon 10) of the UBE3A gene. This alteration results from a C to T substitution at nucleotide position 2480, causing the proline (P) at amino acid position 827 to be replaced by a leucine (L). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration has been reported in multiple unrelated patients with features consistent with Angelman syndrome, including at least one presumed de novo occurrence (Sadikovic, 2014; Xu, 2017; internal data; personal communication). This amino acid position is highly conserved in available vertebrate species. The in silico prediction for this alteration is inconclusive. Based on the available evidence, this alteration is classified as likely pathogenic. (less)
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Pathogenic
(Feb 14, 2014)
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no assertion criteria provided
Method: clinical testing
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Angelman Syndrome
Affected status: yes
Allele origin:
de novo
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Baylor Genetics
Study: UBE3A Mutation Study
Accession: SCV000172066.1 First in ClinVar: Oct 04, 2014 Last updated: Oct 04, 2014
Comment:
Data collected from clinical UBE3A sequence analysis results
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Number of individuals with the variant: 1
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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 |
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[Clinical and genetic analysis of two unrelated patients with Angelman syndrome and novel UBE3A mutations]. | Xu H | Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics | 2017 | PMID: 29188609 |
Mutation Update for UBE3A variants in Angelman syndrome. | Sadikovic B | Human mutation | 2014 | PMID: 25212744 |
Text-mined citations for rs587781239 ...
HelpRecord last updated May 08, 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.