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]

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Variant: NM_000018.4(ACADVL):c.521T>C (p.Val174Ala)

CA8337751

617950 (ClinVar)

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 923608f7-b739-4d0a-a5e9-5359808abc41

HGVS expressions

NM_000018.4:c.521T>C

NM_000018.4(ACADVL):c.521T>C (p.Val174Ala)

NC_000017.11:g.7221581T>C

CM000679.2:g.7221581T>C

NC_000017.10:g.7124900T>C

CM000679.1:g.7124900T>C

NC_000017.9:g.7065624T>C

NG_007975.1:g.6748T>C

NG_008391.2:g.3470A>G

ENST00000356839.10:c.521T>C

ENST00000322910.9:c.*476T>C

ENST00000350303.9:c.455T>C

ENST00000356839.9:c.521T>C

ENST00000543245.6:c.590T>C

ENST00000577191.5:n.598T>C

ENST00000577433.5:n.729T>C

ENST00000577857.5:n.337T>C

ENST00000579286.5:n.702T>C

ENST00000579886.2:c.359T>C

ENST00000580365.1:n.252T>C

ENST00000581378.5:c.239T>C

ENST00000581562.5:n.525-371T>C

ENST00000582166.1:n.502T>C

ENST00000583312.5:c.521T>C

ENST00000583760.1:n.303T>C

NM_000018.3:c.521T>C

NM_001033859.2:c.455T>C

NM_001270447.1:c.590T>C

NM_001270448.1:c.293T>C

NM_001033859.3:c.455T>C

NM_001270447.2:c.590T>C

NM_001270448.2:c.293T>C

Uncertain Significance

PP3 PM2_Supporting

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The NM_000018.4: c.521T>C (p.Val174Ala) in ACADVL is a missense variant predicted to cause substitution of valine by alanine at amino acid 174 (p.Val174Ala). The highest population minor allele frequency in GnomAD v4.0.0 is 0.0001 in African/African American population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). This variant has been reported in the literature in an individual with an abnormal newborn screen who is an apparently heterozygous carrier for the variant (PMID: 24503138), but this information is insufficient to use toward classification. The computational predictor REVEL gives a score of 0.926, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3). Due to limited evidence, this variant is classified as a 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, PP3 (ACADVL VCEP specifications version 1; approved November 9, 2021).

PP3

The computational predictor REVEL gives a score of 0.926, 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 v4.0.0 is 0.0001 in African/African American population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting).

Approved on: 2024-02-27

Published on: 2024-02-27

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