2-110805388-C-T

Position:

• chr2-110805388-C-T

Variant summary

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

The NM_001142807.4(ACOXL):​c.746C>T​(p.Ala249Val) 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. 15/21 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: ACOXL NM_001142807.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.60

Genes affected

ACOXL (HGNC:25621): (acyl-CoA oxidase like) Predicted to enable acyl-CoA oxidase activity; fatty acid binding activity; and flavin adenine dinucleotide binding activity. Predicted to be involved in fatty acid beta-oxidation using acyl-CoA oxidase and lipid homeostasis. Predicted to be located in peroxisomal matrix. Predicted to be active in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

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=0.28826058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACOXL	NM_001142807.4	c.746C>T	p.Ala249Val	missense_variant	9/18	ENST00000439055.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOXL	ENST00000439055.6	c.746C>T	p.Ala249Val	missense_variant	9/18	2	NM_001142807.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jul 14, 2021

The c.746C>T (p.A249V) alteration is located in exon 9 (coding exon 8) of the ACOXL gene. This alteration results from a C to T substitution at nucleotide position 746, causing the alanine (A) at amino acid position 249 to be replaced by a valine (V). 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	0.24
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.83
DEOGEN2	Benign	0.31	T;.;.;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.065
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.61	T;T;T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.4	L;L;L;.
MutationTaster	Benign	0.77	D;D;D
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.2	D;D;D;D
REVEL	Benign	0.25
Sift	Benign	0.53	T;T;T;T
Sift4G	Benign	0.095	T;T;T;T
Polyphen		0.12	B;.;.;.
Vest4		0.37
MutPred		0.55		Loss of ubiquitination at K251 (P = 0.069);Loss of ubiquitination at K251 (P = 0.069);Loss of ubiquitination at K251 (P = 0.069);.;
MVP		0.67
MPC		0.17
ClinPred		0.29	T
GERP RS		4.2
Varity_R		0.11
gMVP		0.16

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: chr2-111562965;