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]

Link to SEPIO compliant JSON-LD document

CA287436447

Gene: ACADVL

Condition: very long chain acyl-CoA dehydrogenase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 12f44e04-9fe5-45bb-89ec-20ccfee8753d

HGVS expressions

NM_001270448.2:c.351C>T

NC_000017.11:g.7221639C>T

CM000679.2:g.7221639C>T

NC_000017.10:g.7124958C>T

CM000679.1:g.7124958C>T

NC_000017.9:g.7065682C>T

NG_007975.1:g.6806C>T

NG_008391.2:g.3412G>A

ENST00000356839.10:c.579C>T

ENST00000322910.9:c.*534C>T

ENST00000350303.9:c.513C>T

ENST00000356839.9:c.579C>T

ENST00000543245.6:c.648C>T

ENST00000577191.5:n.656C>T

ENST00000577433.5:n.787C>T

ENST00000577857.5:n.395C>T

ENST00000579286.5:n.760C>T

ENST00000579886.2:c.417C>T

ENST00000580365.1:n.310C>T

ENST00000581378.5:n.297C>T

ENST00000581562.5:n.525-313C>T

ENST00000583312.5:c.579C>T

ENST00000583760.1:n.361C>T

NM_000018.3:c.579C>T

NM_001033859.2:c.513C>T

NM_001270447.1:c.648C>T

NM_001270448.1:c.351C>T

NM_000018.4:c.579C>T

NM_001033859.3:c.513C>T

NM_001270447.2:c.648C>T

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"

PM2_Supporting BP7 BP4

PM4 PM5 PVS1 BS1 BP3 BP1 PS1 BA1 PP3 PP2

Evidence Links 0

Expert Panel

ACADVL VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

ACADVL VCEP

The c.579C>T (p.Gly193=) variant is a synonymous (silent) variant that is not predicted by Splice AI, MaxEntScn or NNSplice to impact splicing. In addition, it occurs at a nucleotide that is not conserved as shown by phyloP (BP4, BP7). To our knowledge, this variant is not reported in the medical literature. This variant is absent from gnomAD v2.1.1; however, this is not considered conflicting evidence with BP4 and BP7. In summary, this variant meets the criteria to be classified as likely benign 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: BP4, BP7 (ACADVL VCEP specifications version 1; approved November 8, 2021).

PM2_Supporting

c.579C>T was not found in gnomAD

BP7

A 41 basepair region centered on c.579C>T did not give a predicted splice site with NNSPLICE. HumanSplicingFinder was not available for use at this time. SpliceAI gave scores of Acceptor Loss 0.00, Donor Loss 0.01, Acceptor Gain 0.00, Donor Gain 0.05. The nucleotide position is not conserved (100 vertebrates Basewise Conservation by PhyloP (phyloP100way) score was only 0.805992 on UCSC genome browser GRCh38).

BP4

c.579C is not conserved, no computational evidence of variant impact on protein

PM4

Variant is not an indel

PM5

c.579C>T is silent, not missense

PVS1

c.579C>T is silent codon change and does not meet any PVS1 criteria

BS1

c.579C>T was not found in gnomAD

BP3

Variant is not an indel

BP1

c.579C>T is silent, not missense

PS1

c.579C>T is silent, not missense

BA1

c.579C>T was not found in gnomAD

PP3

c.579C>T is silent, not missense

PP2

c.579C>T is silent, not missense

Approved on: 2023-02-13

Published on: 2023-02-13

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