Variant: NM_014297.5(ETHE1):c.197A>G (p.Lys66Arg)

CA9487931

329444 (ClinVar)

Gene: ETHE1

Condition: ethylmalonic encephalopathy

Inheritance Mode: Autosomal recessive inheritance

UUID: de6ef8a7-803e-4b9d-8f46-fe0d6be86f09

Approved on: 2020-08-18

Published on: 2021-10-22

HGVS expressions

NM_014297.5:c.197A>G
NM_014297.5(ETHE1):c.197A>G (p.Lys66Arg)
NC_000019.10:g.43526544T>C
CM000681.2:g.43526544T>C
NC_000019.9:g.44030696T>C
CM000681.1:g.44030696T>C
NC_000019.8:g.48722536T>C
NG_008141.1:g.5701A>G
ENST00000292147.7:c.197A>G
ENST00000292147.6:c.197A>G
ENST00000458714.2:c.53T>C
ENST00000594342.5:c.197A>G
ENST00000595115.1:n.250A>G
ENST00000598330.1:c.197A>G
ENST00000600651.5:c.197A>G
ENST00000602138.1:c.*201A>G
NM_014297.3:c.197A>G
NM_001320867.1:c.197A>G
NM_001320868.1:c.-24A>G
NM_001320869.1:c.81+553A>G
NM_014297.4:c.197A>G
NM_001320867.2:c.197A>G
NM_001320868.2:c.-24A>G
NM_001320869.2:c.81+553A>G

Uncertain Significance

• Met criteria codes: BS1

• Not Met criteria codes: PS4 PS3 PS1 PP3 PM5 BA1 BS3 BS2 BP5 BP4

Expert Panel

Mitochondrial Diseases VCEP

Criteria Specification Information

Evidence submitted by expert panel

Mitochondrial Diseases VCEP

This variant was classified as a variant of uncertain significance as there has not been sufficient evidence to support either a benign or a pathogenic classification. Specifically, this variant has not been reported in the literature in affected or unaffected patients, has no published functional data. This variant is present in population databases with an allele frequency of 0.02%, which is higher allele frequency expected for a pathogenic variant in ETHE1 (BS1). However, not enough criteria were met to support a pathogenic or benign classification.

Met criteria codes

• BS1: Allele frequency reported as 0.0002 which is higher than the proposed cutoff of 0.01% to meet BS1 criteria.

Not Met criteria codes

• PS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS3: No published functional studies demonstrating the variant's impact on protein function
• PS1: 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
• PM5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS3: No published functional studies demonstrating the variant's impact on protein function
• BS2: Not observed in a healthy or affected individual
• BP5: Not observed in a healthy or affected individual
• BP4: REVEL score is 0.205 (mustbe less than 0.15 to meet criteria)