ACADVL p.Gly523Arg

Variant names:

• chr17-7224355-G-C
• NM_000018.4:c.1567G>C
• ACADVL p.Gly523Arg

Your query was ambiguous. Multiple possible variants found:

• chr17-7224355-G-C
• chr17-7224355-G-A
• chr17-7224355-GGA-CGT
• chr17-7224355-GGA-CGC
• chr17-7224355-GGA-CGG
• chr17-7224355-GGA-AGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000018.4(ACADVL):​c.1567G>C​(p.Gly523Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. G523G) has been classified as Likely benign. The gene ACADVL is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACADVL NM_000018.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.07
• Publications: 0 publications found

Genes affected

ACADVL (HGNC:92): (acyl-CoA dehydrogenase very long chain) The protein encoded by this gene is targeted to the inner mitochondrial membrane where it catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. This acyl-Coenzyme A dehydrogenase is specific to long-chain and very-long-chain fatty acids. A deficiency in this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACADVL Gene-Disease associations (from GenCC):

• very long chain acyl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Specifications for ACADVL are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000018.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADVL	NM_000018.4	MANE Select	c.1567G>C	p.Gly523Arg	missense	Exon 16 of 20	NP_000009.1	P49748-1
	ACADVL	NM_001270447.2		c.1636G>C	p.Gly546Arg	missense	Exon 17 of 21	NP_001257376.1	P49748-3
	ACADVL	NM_001033859.3		c.1501G>C	p.Gly501Arg	missense	Exon 15 of 19	NP_001029031.1	P49748-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADVL	ENST00000356839.10	TSL:1 MANE Select	c.1567G>C	p.Gly523Arg	missense	Exon 16 of 20	ENSP00000349297.5	P49748-1
	ACADVL	ENST00000350303.9	TSL:1	c.1501G>C	p.Gly501Arg	missense	Exon 15 of 19	ENSP00000344152.5	P49748-2
	ACADVL	ENST00000543245.6	TSL:2	c.1636G>C	p.Gly546Arg	missense	Exon 17 of 21	ENSP00000438689.2	P49748-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Benign	20
DANN	Benign	0.73
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.087
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.40	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		6.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.49
Sift	Benign	0.040	D
Sift4G	Benign	0.10	T
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.21
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-7127674;