2-210192853-C-T

Position:

• chr2-210192853-C-T

Variant summary

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

The ENST00000233710.4(ACADL):​c.1150G>A​(p.Val384Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACADL ENST00000233710.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.52

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACADL	NM_001608.4	c.1150G>A	p.Val384Ile	missense_variant	10/11	ENST00000233710.4	NP_001599.1
ACADL	XM_005246517.5	c.1087G>A	p.Val363Ile	missense_variant	10/11		XP_005246574.1
ACADL	XM_047444103.1	c.727G>A	p.Val243Ile	missense_variant	10/11		XP_047300059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACADL	ENST00000233710.4	c.1150G>A	p.Val384Ile	missense_variant	10/11	1	NM_001608.4	ENSP00000233710	P1
	ENST00000639259.2	n.279+21024C>T		intron_variant, non_coding_transcript_variant		5
ACADL	ENST00000652584.1	n.1378G>A		non_coding_transcript_exon_variant	10/11
	ENST00000412065.1	n.312+21024C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2024

The c.1150G>A (p.V384I) alteration is located in exon 10 (coding exon 10) of the ACADL gene. This alteration results from a G to A substitution at nucleotide position 1150, causing the valine (V) at amino acid position 384 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.094
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.060	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.024	D
Polyphen		0.41	B
Vest4		0.28
MutPred		0.64		Loss of catalytic residue at V384 (P = 0.1729);
MVP		0.87
MPC		0.25
ClinPred		0.86	D
GERP RS		4.2
Varity_R		0.086
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr2-211057577;