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_014297.5(ETHE1):c.712+181A>G

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA308740635

671647 (ClinVar)

Gene: ETHE1

Condition: ethylmalonic encephalopathy

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 29d7a907-0367-403f-a949-666538359d42

Approved on: 2021-05-07

Published on: 2021-05-07

HGVS expressions

NM_014297.5:c.712+181A>G

NM_014297.5(ETHE1):c.712+181A>G

ENST00000292147.7:c.712+181A>G

ENST00000292147.6:c.712+181A>G

ENST00000594342.5:c.*275+181A>G

ENST00000598330.1:c.*456A>G

ENST00000600651.5:c.*110A>G

NM_014297.3:c.712+181A>G

NM_001320867.1:c.679+181A>G

NM_001320868.1:c.343+181A>G

NM_001320869.1:c.418+181A>G

NM_014297.4:c.712+181A>G

NM_001320867.2:c.679+181A>G

NM_001320868.2:c.343+181A>G

NM_001320869.2:c.418+181A>G

NC_000019.10:g.43507763T>C

CM000681.2:g.43507763T>C

NC_000019.9:g.44011915T>C

CM000681.1:g.44011915T>C

NC_000019.8:g.48703755T>C

NG_008141.1:g.24482A>G

Benign

BS2 BP7 BA1

PM2

Evidence Links 0

Expert Panel

Mitochondrial Diseases VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Mitochondrial Diseases VCEP

The allele frequency of the c.712+181A>G variant in the ETHE1 gene is reported as >12% in gnomAD, including 167 homozygotes, which is high enough to be classified as benign based on thresholds defined by the ClinGen ETHE1 Variant Curation Expert Panel (>0.1% in gnomAD- BA1 and BS2). In silico splicing predictors (Splice AI) for this intronic variant do not predict a deleterious effect (BP7). In summary, this variant meets criteria to be classified as benign for ETHE1-related ethylmalonic encephalopathy. ETHE1-specific ACMG/AMP criteria applied: (BA1, BS2, BP7).

BS2

167 homozygotes in gnomAD

BP7

This is an intronic variant. Splice AI score does not suggest this variant alters splicing. Splice AI score of 0.00 for acceptor gain and loss and 0.00 for donor gain and donor loss.

BA1

Allele Frequency is reported as >12% which is higher than the cutoff proposed for ETHE1 variants of 0.1%

PM2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

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