dbSNP rs63750670: ACADVL:p.Gln13Glu (chr17-7220021-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000018.4(ACADVL):c.37C>G(p.Gln13Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,078 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ACADVL
NM_000018.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.27

Variant links:

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 links:

DLG4 (HGNC:2903): (discs large MAGUK scaffold protein 4) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DLG4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.3663705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADVL	NM_000018.4 link	c.37C>G	p.Gln13Glu	missense_variant	Exon 1 of 20	ENST00000356839.10	NP_000009.1	P49748-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACADVL	ENST00000356839.10 link	c.37C>G	p.Gln13Glu	missense_variant	Exon 1 of 20	1	NM_000018.4	ENSP00000349297.5		P49748-1
DLG4	ENST00000648172.8 link	c.-1172G>C		upstream_gene_variant				ENSP00000497806.3		P78352-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453078

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722922

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.17

T;.;.;.;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.83

T;T;T;T;T

M_CAP

Pathogenic

0.29

MetaRNN

Benign

0.37

T;T;T;T;T

MetaSVM

Uncertain

0.55

MutationAssessor

Uncertain

2.4

M;.;M;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.38

.;.;N;.;.

REVEL

Uncertain

0.30

Sift

Uncertain

0.019

.;.;D;.;.

Sift4G

Benign

0.38

T;D;T;D;D

Polyphen

0.65

P;.;P;.;.

Vest4

0.45

MutPred

0.25

Gain of methylation at R12 (P = 0.1144);Gain of methylation at R12 (P = 0.1144);Gain of methylation at R12 (P = 0.1144);Gain of methylation at R12 (P = 0.1144);Gain of methylation at R12 (P = 0.1144);

MVP

0.97

ClinPred

0.63

GERP RS

4.9

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

4.0

Varity_R

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over