Variant: NM_000018.4(ACADVL):c.482C>T (p.Ala161Val)

CA312251

203572 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: cb368f3f-6c64-4fd4-8254-eab4117a74ea

Approved on: 2024-08-13

Published on: 2024-08-13

HGVS expressions

NM_000018.4:c.482C>T
NM_000018.4(ACADVL):c.482C>T (p.Ala161Val)
NC_000017.11:g.7221542C>T
CM000679.2:g.7221542C>T
NC_000017.10:g.7124861C>T
CM000679.1:g.7124861C>T
NC_000017.9:g.7065585C>T
NG_007975.1:g.6709C>T
NG_008391.2:g.3509G>A
ENST00000356839.10:c.482C>T
ENST00000322910.9:c.*437C>T
ENST00000350303.9:c.416C>T
ENST00000356839.9:c.482C>T
ENST00000543245.6:c.551C>T
ENST00000577191.5:n.559C>T
ENST00000577433.5:n.690C>T
ENST00000577857.5:n.298C>T
ENST00000579286.5:n.663C>T
ENST00000579886.2:c.320C>T
ENST00000580365.1:n.213C>T
ENST00000581378.5:c.200C>T
ENST00000581562.5:n.525-410C>T
ENST00000582166.1:n.463C>T
ENST00000583312.5:c.482C>T
ENST00000583760.1:n.264C>T
NM_000018.3:c.482C>T
NM_001033859.2:c.416C>T
NM_001270447.1:c.551C>T
NM_001270448.1:c.254C>T
NM_001033859.3:c.416C>T
NM_001270447.2:c.551C>T
NM_001270448.2:c.254C>T

Uncertain Significance

• Met criteria codes: PP3 PM2_Supporting PM5_Supporting

• Not Met criteria codes: PM1

Expert Panel

ACADVL VCEP

Criteria Specification Information

Evidence submitted by expert panel

ACADVL VCEP

The c.482C>T (NM_000018.4) variant in ACADVL is a missense variant predicted to cause substitution of alanine by valine at amino acid 161 (p.Ala161Val). The highest population minor allele frequency in gnomAD v2.1.1 is 0.000001313 in European (non-Finnish) 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 0.77, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3). Another missense variant, c.481G>A (p.Ala161Thr), in the same codon has been classified as likely pathogenic for very long chain acyl CoA dehydrogenase (VLCAD) deficiency by the ClinGen ACADVL Variant Curation Expert Panel (PM5_supporting). Due to limited evidence, this variant is classified as a variant of uncertain significance for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PM2_Supporting, PM5_Supporting, PP3 (ACADVL VCEP specifications version 1; approved November 9, 2021)

Met criteria codes

• PP3: The computational predictor REVEL gives a score of 0.77, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3).
• PM2_Supporting: The highest population minor allele frequency in gnomAD v2.1.1 is 0.000001313 in European (non-Finnish) population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting).
• PM5_Supporting: p.Ala161Thr approved as likely pathogenic

Not Met criteria codes

• PM1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline