2-110933494-C-T

Variant summary

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

The NM_001142807.4(ACOXL):c.911C>T(p.Ala304Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACOXL NM_001142807.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.83

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACOXL	NM_001142807.4	c.911C>T	p.Ala304Val	missense_variant	12/18	ENST00000439055.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOXL	ENST00000439055.6	c.911C>T	p.Ala304Val	missense_variant	12/18	2	NM_001142807.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Oct 26, 2022

The c.911C>T (p.A304V) alteration is located in exon 12 (coding exon 11) of the ACOXL gene. This alteration results from a C to T substitution at nucleotide position 911, causing the alanine (A) at amino acid position 304 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	0.18
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.082
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.24	N;N;.
MutationTaster	Benign	0.99	D;D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.11	N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.33	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.025	B;.;.
Vest4		0.66
MutPred		0.69		Loss of catalytic residue at A304 (P = 0.0675);Loss of catalytic residue at A304 (P = 0.0675);.;
MVP		0.85
MPC		0.66
ClinPred		0.79	D
GERP RS		4.6
Varity_R		0.082
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: chr2-111691071;