Variant: NM_014297.4(ETHE1):c.378G>A (p.Ala126=)

CA9487866

379605 (ClinVar)

Gene: ETHE1

Condition: ethylmalonic encephalopathy

Inheritance Mode: Autosomal recessive inheritance

UUID: 98027f68-f325-465f-995f-3d43c584a681

Approved on: 2020-08-18

Published on: 2021-10-22

HGVS expressions

NM_014297.4:c.378G>A
NM_014297.4(ETHE1):c.378G>A (p.Ala126=)
NC_000019.10:g.43511564C>T
CM000681.2:g.43511564C>T
NC_000019.9:g.44015716C>T
CM000681.1:g.44015716C>T
NC_000019.8:g.48707556C>T
NG_008141.1:g.20681G>A
ENST00000292147.7:c.378G>A
ENST00000292147.6:c.378G>A
ENST00000594342.5:c.229G>A
ENST00000598330.1:c.229G>A
ENST00000600651.5:c.378G>A
ENST00000602138.1:c.*382G>A
NM_014297.3:c.378G>A
NM_001320867.1:c.345G>A
NM_001320868.1:c.9G>A
NM_001320869.1:c.84G>A
NM_014297.5:c.378G>A
NM_001320867.2:c.345G>A
NM_001320868.2:c.9G>A
NM_001320869.2:c.84G>A
NM_014297.5(ETHE1):c.378G>A (p.Ala126=)

Benign

• Met criteria codes: BA1 BS2 BP7

• Not Met criteria codes: BS4 BS3 BP5 BP2 BP4 PS2 PS4 PS3 PS1 PP1 PP4 PP3 PM3 PM1 PM5 PM6 PM2

Expert Panel

Mitochondrial Diseases VCEP

Criteria Specification Information

Evidence submitted by expert panel

Mitochondrial Diseases VCEP

The filtering allele frequency of the c.378G>A variant in the ETHE1 gene is >0.2% by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Mito Variant Curation Expert Panel (BA1)

Met criteria codes

• BA1: Allele frequency has per ExAC is estimated to be 0.00262 which is higher than cutoff proposed for ETHE1 variants of 0.001.
• BS2: Individual reported homzygous for variant in gnomAD.
• BP7: This mutations is confirmed as a synonymous missense mutation.

Not Met criteria codes

• BS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP4: Data is only available from one computational predictor (CADD) which supports benign classification.
• PS2: This condition is inherited in an autosomal recessive manner and is penetrant
• PS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM1: ETHE1 is a small gene with no established hot spots
• PM5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM6: This condition is inherited in an autosomal recessive manner, with no reports of de novo variants
• PM2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline