Evidence Repository
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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  • No ClinVar Id was directly found from the curated document
  • See Evidence submitted by expert panel for details.

Variant: NM_000018.4:c.494A>T

CA397723028

Gene: ACADVL
Condition: very long chain acyl-CoA dehydrogenase deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 95fa79f7-4e11-46d1-aa57-b128e34a8b39

HGVS expressions

NM_000018.4:c.494A>T
NC_000017.11:g.7221554A>T
CM000679.2:g.7221554A>T
NC_000017.10:g.7124873A>T
CM000679.1:g.7124873A>T
NC_000017.9:g.7065597A>T
NG_007975.1:g.6721A>T
NG_008391.2:g.3497T>A
ENST00000356839.10:c.494A>T
ENST00000322910.9:c.*449A>T
ENST00000350303.9:c.428A>T
ENST00000356839.9:c.494A>T
ENST00000543245.6:c.563A>T
ENST00000577191.5:n.571A>T
ENST00000577433.5:n.702A>T
ENST00000577857.5:n.310A>T
ENST00000579286.5:n.675A>T
ENST00000579886.2:c.332A>T
ENST00000580365.1:n.225A>T
ENST00000581378.5:n.212A>T
ENST00000581562.5:n.525-398A>T
ENST00000582166.1:n.475A>T
ENST00000583312.5:c.494A>T
ENST00000583760.1:n.276A>T
NM_000018.3:c.494A>T
NM_001033859.2:c.428A>T
NM_001270447.1:c.563A>T
NM_001270448.1:c.266A>T
NM_001033859.3:c.428A>T
NM_001270447.2:c.563A>T
NM_001270448.2:c.266A>T

Uncertain Significance

Met criteria codes 2
PM2_Supporting PP3
Not Met criteria codes 4
PM5 PM1 BS1 BA1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
ACADVL VCEP
The c.494A>T variant in ACADVL is a missense variant predicted to cause substitution of glutamic acid by valine at amino acid 165 (p.Glu165Val). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.934, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3). A palmitoyl-CoA oxidation assay in patient-derived lymphocytes from an individual carrying this variant and no other identified ACADVL variant showed 40% reduced residual assay (PMID: 30194637). However, this assay does not meet the requirements for use by the ClinGen ACADVL Variant Curation Expert Panel. In summary, this variant meets the criteria to be 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 (VCEP specifications v2.0, approved on 09/16/2021).
Met criteria codes
PM2_Supporting
c.494A>T (p.Glu165Val) is not found in population databases.
PP3
Revel score (0.934) is >.75 so PP3 is met per VCEP guidelines.
Not Met criteria codes
PM5
Other Missense changes at this residue (p.Glu165) have been seen but are not determined to be pathogenic (i.e. p.Glu165Lys, p.Glu165Asp, p.Glu165=).
PM1
This residue not determined to be in a currently known mutational hot spot or well established functional domain per VCEP criteria.
BS1
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
Approved on: 2022-03-08
Published on: 2022-03-08
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