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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Variant: NM_000018.4(ACADVL):c.439C>T (p.Pro147Ser)

CA287435425

557575 (ClinVar)

Gene: ACADVL
Condition: very long chain acyl-CoA dehydrogenase deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: a4fbfcb5-4511-48ef-b1a6-5e1adac97320
Approved on: 2022-09-22
Published on: 2022-09-22

HGVS expressions

NM_000018.4:c.439C>T
NM_000018.4(ACADVL):c.439C>T (p.Pro147Ser)
NC_000017.11:g.7221020C>T
CM000679.2:g.7221020C>T
NC_000017.10:g.7124339C>T
CM000679.1:g.7124339C>T
NC_000017.9:g.7065063C>T
NG_007975.1:g.6187C>T
NG_008391.2:g.4031G>A
ENST00000356839.10:c.439C>T
ENST00000322910.9:c.*394C>T
ENST00000350303.9:c.373C>T
ENST00000356839.9:c.439C>T
ENST00000543245.6:c.508C>T
ENST00000577191.5:n.516C>T
ENST00000577433.5:n.647C>T
ENST00000577857.5:n.293+190C>T
ENST00000579286.5:n.620C>T
ENST00000579886.2:c.277C>T
ENST00000580365.1:n.170C>T
ENST00000581378.5:n.138C>T
ENST00000581562.5:n.486C>T
ENST00000582056.5:n.622C>T
ENST00000582166.1:n.420C>T
ENST00000583312.5:c.439C>T
ENST00000584103.5:c.472C>T
NM_000018.3:c.439C>T
NM_001033859.2:c.373C>T
NM_001270447.1:c.508C>T
NM_001270448.1:c.211C>T
NM_001033859.3:c.373C>T
NM_001270447.2:c.508C>T
NM_001270448.2:c.211C>T
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Uncertain Significance

Met criteria codes 4
PM3_Supporting PM2_Supporting PP4 PP3
Not Met criteria codes 3
PM5 PM1 PS1

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
ACADVL VCEP
The c.439C>T (p.Pro147Ser) variant in ACADVL is a missense in exon 6. This variant has been reported once in the literature in a proband with very-long chain acyl-CoA dehydrogenase deficiency, and elevated C14:1 in NBS (PP4, PMID27209629). This variant is absent from population databases gnomAD v2.1.1 (PM2_supporting). The computational predictor REVEL gives a score of 0.88, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3). However, there is insufficient experimental or case data identified in the literature for this variant and is therefore classified as a VUS. (ACADVL-specific ACMG/AMP criteria applied: PP4; PM2_supporting; PP3).
Met criteria codes
PM3_Supporting
Unconfirmed trans with p.Ser319Ter, applied 0.5 points evaluating this second variant as pathogenic
PM2_Supporting
Absent from gnomAD
PP4
NBS C14:1 uM = 2.76, follow-up plasma acylcarnitine profile was reported to be within normal range, enzyme activity not assessed (PMID27209629).
PP3
Revel score 0.879 (above 0.75 threshold)
Not Met criteria codes
PM5
No alternative missense change at this residue that is determined to be pathogenic.
PM1
P147 stabilizes a loop that is away from the active site, but still can impact protein structure integrity (PMID 27209629). This residue is not identified to be a mutational hotspot or well established functional domain per VECP criteria.
P147 stabilizes a loop that is away from the active site, but still can impact protein structure integrity (PMID 27209629). PubMed:27209629
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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