Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_130839.5(UBE3A):c.199A>G (p.Ile67Val)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA294734

156677 (ClinVar)

Gene: UBE3A

Condition: Angelman syndrome

Inheritance Mode: Autosomal dominant inheritance (with paternal imprinting (HP:0012274))

Link to MONDO

UUID: 1b5e8707-cc5d-44b9-a199-951bf5d65b18

Approved on: 2022-06-30

Published on: 2022-06-30

HGVS expressions

NM_130839.5:c.199A>G

NM_130839.5(UBE3A):c.199A>G (p.Ile67Val)

NC_000015.10:g.25375627T>C

CM000677.2:g.25375627T>C

NC_000015.9:g.25620774T>C

CM000677.1:g.25620774T>C

NC_000015.8:g.23171867T>C

NG_009268.1:g.68355A>G

ENST00000438097.6:c.139A>G

ENST00000625778.3:c.139A>G

ENST00000635914.1:c.139A>G

ENST00000637886.1:c.199A>G

ENST00000638011.1:c.139A>G

ENST00000638155.1:c.139A>G

ENST00000648336.2:c.199A>G

ENST00000649550.1:c.139A>G

ENST00000650110.1:c.208A>G

ENST00000675000.1:n.874A>G

ENST00000675038.1:n.934A>G

ENST00000675177.1:c.22A>G

ENST00000675593.1:n.2895A>G

ENST00000232165.7:c.139A>G

ENST00000397954.6:c.208A>G

ENST00000428984.6:c.139A>G

ENST00000438097.5:c.139A>G

ENST00000566215.5:c.139A>G

ENST00000614096.4:c.199A>G

ENST00000625778.2:c.139A>G

ENST00000626068.2:c.220A>G

ENST00000626793.2:n.310-60A>G

ENST00000628267.2:c.139A>G

ENST00000628733.2:c.199A>G

ENST00000629252.2:c.139A>G

ENST00000629886.2:c.199A>G

ENST00000630424.2:c.139A>G

ENST00000630607.2:c.139A>G

ENST00000630907.2:c.199A>G

NM_000462.3:c.208A>G

NM_130838.1:c.139A>G

NM_130839.2:c.199A>G

NM_000462.5:c.208A>G

NM_001354505.1:c.199A>G

NM_001354506.1:c.139A>G

NM_001354507.1:c.139A>G

NM_001354508.1:c.139A>G

NM_001354509.1:c.139A>G

NM_001354511.1:c.139A>G

NM_001354512.1:c.139A>G

NM_001354513.1:c.139A>G

NM_001354523.1:c.139A>G

NM_001354526.1:c.139A>G

NM_001354538.1:c.199A>G

NM_001354539.1:c.139A>G

NM_001354540.1:c.139A>G

NM_001354541.1:c.139A>G

NM_001354542.1:c.139A>G

NM_001354543.1:c.139A>G

NM_001354544.1:c.139A>G

NM_001354545.1:c.199A>G

NM_001354546.1:c.22A>G

NM_001354547.1:c.139A>G

NM_001354548.1:c.139A>G

NM_001354549.1:c.139A>G

NM_001354550.1:c.199A>G

NM_001354551.1:c.139A>G

NM_130838.3:c.139A>G

NM_130839.4:c.199A>G

NR_146177.1:n.18393-15969T>C

NR_148916.1:n.747A>G

NM_001354506.2:c.139A>G

NM_001354507.2:c.139A>G

NM_001354508.2:c.139A>G

NM_001354509.2:c.139A>G

NM_001354511.2:c.139A>G

NM_001354512.2:c.139A>G

NM_001354513.2:c.139A>G

NM_001354523.2:c.139A>G

NM_001354538.2:c.199A>G

NM_001354539.2:c.139A>G

NM_001354540.2:c.139A>G

NM_001354541.2:c.139A>G

NM_001354542.2:c.139A>G

NM_001354543.2:c.139A>G

NM_001354544.2:c.139A>G

NM_001354545.2:c.199A>G

NM_001354546.2:c.22A>G

NM_001354547.2:c.139A>G

NM_001354548.2:c.139A>G

NM_001354549.2:c.139A>G

NM_001354550.2:c.199A>G

NM_001354551.2:c.139A>G

NM_001374461.1:c.139A>G

NM_130838.4:c.139A>G

NR_148916.2:n.715A>G

Uncertain Significance

BP4

BS1 PP4 PM2 PS4

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The c.139A>G p.(Ile47Val) variant in UBE3A (NM_130838.2) is present in gnomAD v2.1.1 at a frequency of 0.00088% in the European non-Finnish sub population (no criteria met). The p.(Ile47Val) variant has been observed in at least 3 individuals with neurodevelopmental phenotypes consistent with UBE3A-related disease (ClinVar SCV000191055.4, SCV001445014.1); however, PS4 cannot be applied due to the gnomAD frequency. Computational analysis prediction tools suggest that the p.(Ile47Val) variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the c.139A>G p.(Ile47Val) variant in UBE3A is classified as a Variant of Uncertain Significance based on the ACMG/AMP criteria (BP4).

BP4

Computational analysis prediction tools suggest that the p.Ile47Val variant does not have a deleterious impact; however this information does not predict clinical significance on its own.

BS1

The p.Ile47Val variant in UBE3A is present in gnomAD v2.1.1 at a frequency of 0.00088% in the European non-Finnish sub population (no criteria met).

PP4

Identified in external laboratories however the clinical details provided for these patients is insufficient to apply PP4.

PM2

The p.Ile47Val variant in UBE3A is present in gnomAD v2.1.1 at a frequency of 0.00088% in the European non-Finnish sub population (no criteria met).

PS4

The p.Ile47Val variant has been observed in at least 3 individuals with neurodevelopmental phenotypes consistent with UBE3A-related disease (ClinVar SCV000191055.4; SCV001445014.1), however the PS4 criteria cannot be applied due to this variant being detected in 1 heterozygote in gnomAD.

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.