2-210203359-G-C

Variant names:

• chr2-210203359-G-C
• rs1247727498
• NM_001608.4:c.956C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001608.4(ACADL):​c.956C>G​(p.Ala319Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: ACADL NM_001608.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.18

Genes affected

ACADL (HGNC:88): (acyl-CoA dehydrogenase long chain) The protein encoded by this gene belongs to the acyl-CoA dehydrogenase family, which is a family of mitochondrial flavoenzymes involved in fatty acid and branched chain amino-acid metabolism. This protein is one of the four enzymes that catalyze the initial step of mitochondrial beta-oxidation of straight-chain fatty acid. Defects in this gene are the cause of long-chain acyl-CoA dehydrogenase (LCAD) deficiency, leading to nonketotic hypoglycemia. [provided by RefSeq, Jul 2008]

ENSG00000279317 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.932

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACADL	NM_001608.4	c.956C>G	p.Ala319Gly	missense_variant	Exon 8 of 11	ENST00000233710.4	NP_001599.1
ACADL	XM_005246517.5	c.893C>G	p.Ala298Gly	missense_variant	Exon 8 of 11		XP_005246574.1
ACADL	XM_047444103.1	c.533C>G	p.Ala178Gly	missense_variant	Exon 8 of 11		XP_047300059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACADL	ENST00000233710.4	c.956C>G	p.Ala319Gly	missense_variant	Exon 8 of 11	1	NM_001608.4	ENSP00000233710.3
ACADL	ENST00000652584.1	n.1184C>G		non_coding_transcript_exon_variant	Exon 8 of 11
ENSG00000279317	ENST00000412065.1	n.313-15113G>C		intron_variant	Intron 1 of 2	4
ENSG00000279317	ENST00000639259.2	n.280-26924G>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74352

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000540 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.93	D
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.1	H
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-3.9	D
REVEL	Pathogenic	0.95
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.77		Gain of disorder (P = 0.0652);
MVP		0.99
MPC		0.84
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.93
gMVP		0.62

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: rs1247727498; hg19: chr2-211068083;