rs2230179

Variant names:

• chr17-7220033-C-A
• NM_000018.4:c.49C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-7220033-C-A
• chr17-7220033-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000018.4(ACADVL):​c.49C>A​(p.Leu17Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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: 0.0000014 (0 hom.)
• Consequence: ACADVL NM_000018.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.916

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1188412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADVL	NM_000018.4	c.49C>A	p.Leu17Ile	missense_variant	Exon 1 of 20	ENST00000356839.10	NP_000009.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACADVL	ENST00000356839.10	c.49C>A	p.Leu17Ile	missense_variant	Exon 1 of 20	1	NM_000018.4	ENSP00000349297.5
DLG4	ENST00000648172.8	c.-1184G>T		upstream_gene_variant				ENSP00000497806.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1452620 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 722688

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	6.5
DANN	Benign	0.91
DEOGEN2	Benign	0.13	T;.;.;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.69	T;T;T;T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Uncertain	2.3	M;.;M;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.33	.;.;N;.;.
REVEL	Benign	0.21
Sift	Benign	0.073	.;.;T;.;.
Sift4G	Benign	0.13	T;T;T;T;T
Polyphen		0.019	B;.;B;.;.
Vest4		0.35
MutPred		0.15		Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);
MVP		0.55
ClinPred		0.49	T
GERP RS		-4.7
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.061

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7123352;