chr17-7224488-G-G

Variant names:

• chr17-7224488-G-G
• NM_000018.4:c.

Variant summary

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

The NM_000018.4(ACADVL):​c. variant causes a exon region 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. The gene ACADVL is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACADVL NM_000018.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.60
• 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.		exon_region	Exon 13 of 20	NP_000009.1	P49748-1
	ACADVL	NM_001270447.2		c.		exon_region	Exon 14 of 21	NP_001257376.1	P49748-3
	ACADVL	NM_001033859.3		c.		exon_region	Exon 12 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.		exon_region	Exon 20 of 20	ENSP00000349297.5	P49748-1
	ACADVL	ENST00000350303.9	TSL:1	c.		exon_region	Exon 19 of 19	ENSP00000344152.5	P49748-2
	ACADVL	ENST00000356839.10	TSL:1 MANE Select	c.		3_prime_UTR	Exon 20 of 20	ENSP00000349297.5	P49748-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.6

Splicing

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: chr17-7127807;