17-7220145-G-T

Position:

• chr17-7220145-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000018.4(ACADVL):​c.86G>T​(p.Gly29Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACADVL NM_000018.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35317892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACADVL	NM_000018.4	c.86G>T	p.Gly29Val	missense_variant	2/20	ENST00000356839.10	NP_000009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADVL	ENST00000356839.10	c.86G>T	p.Gly29Val	missense_variant	2/20	1	NM_000018.4	ENSP00000349297.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	.;T;.;.;.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.039
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.84	T;T;T;T;T;D
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.35	T;T;T;T;T;T
MetaSVM	Uncertain	0.77	D
MutationAssessor	Benign	1.9	.;M;.;M;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.66	N;N;.;N;.;.
REVEL	Uncertain	0.37
Sift	Uncertain	0.0040	D;D;.;D;.;.
Sift4G	Uncertain	0.036	D;D;D;T;D;D
Polyphen		0.025, 0.0030	.;B;.;B;.;.
Vest4		0.47
MutPred		0.16		.;Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP		0.96
MPC		0.75
ClinPred		0.87	D
GERP RS		4.7
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.1
Varity_R		0.17
gMVP		0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs1247979958; hg19: chr17-7123464;