Variant: NM_000018.4(ACADVL):c.1239A>G (p.Ile413Met)

CA8338045

474879 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: b6ba1288-887b-4b5b-a7f5-2c086e1688bc

Approved on: 2025-06-10

Published on: 2025-06-10

HGVS expressions

NM_000018.4:c.1239A>G
NM_000018.4(ACADVL):c.1239A>G (p.Ile413Met)
NC_000017.11:g.7223700A>G
CM000679.2:g.7223700A>G
NC_000017.10:g.7127019A>G
CM000679.1:g.7127019A>G
NC_000017.9:g.7067743A>G
NG_007975.1:g.8867A>G
NG_008391.2:g.1351T>C
NG_033038.1:g.15845T>C
ENST00000356839.10:c.1239A>G
ENST00000322910.9:c.*1194A>G
ENST00000350303.9:c.1173A>G
ENST00000356839.9:c.1239A>G
ENST00000542255.6:c.97A>G
ENST00000543245.6:c.1308A>G
ENST00000578579.2:n.410A>G
ENST00000578711.1:n.196A>G
ENST00000578824.5:n.655A>G
ENST00000579425.5:n.263A>G
ENST00000579546.1:c.76A>G
ENST00000583850.5:n.14A>G
ENST00000583858.5:c.268A>G
ENST00000585203.6:n.447A>G
NM_000018.3:c.1239A>G
NM_001033859.2:c.1173A>G
NM_001270447.1:c.1308A>G
NM_001270448.1:c.1011A>G
NM_001033859.3:c.1173A>G
NM_001270447.2:c.1308A>G
NM_001270448.2:c.1011A>G

Uncertain Significance

• Met criteria codes: PM2

• Not Met criteria codes: PP3 PM3 PM1

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specification: ClinGen ACADVL Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ACADVL Version 2.0.0

Evidence submitted by expert panel

ACADVL VCEP

The NM_000018.4(ACADVL):c.1239A>G (p.Ile413Met) in ACADVL is a missense variant predicted to cause substitution of arginine by glutamine at amino acid 613. The highest population minor allele frequency in gnomAD v4.1 is 0.00006 in Admixed American population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.675 which is neither above nor below the thresholds predicting a damaging or benign impact on ACADVL function. This variant does not reside within a region of ACADVL that is defined as a mutational hotspot or critical functional domain by the ClinGen ACADVL Variant Curation Expert Panel. To our knowledge, this variant has not been reported in the literature in any individuals with autosomal recessive very long chain acyl-CoA dehydrogenase (VLCAD) deficiency. In summary, this variant meets the criteria to be classified as variant of uncertain significance for autosomal recessive very long chain acyl-CoA dehydrogenase (VLCAD) deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PM2_Supporting (ACADVL VCEP specifications version 2; approved May 1, 2025).

Met criteria codes

• PM2: The highest population minor allele frequency in gnomAD v4.1 is 0.00006 in East Asian population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting).

Not Met criteria codes

• PP3: The computational predictor REVEL gives a score of 0.675 which is neither above nor below the thresholds predicting a damaging or benign impact on ACADVL function.
• PM3: To our knowledge, this variant has not been reported in the literature in any individuals with autosomal recessive very long chain acyl-CoA dehydrogenase (VLCAD) deficiency.
• PM1: This variant does not reside within a region of ACADVL that is defined as a mutational hotspot or critical functional domain by the ClinGen ACADVL Variant Curation Expert Panel.