2-110784804-A-G

Position:

• chr2-110784804-A-G

Variant summary

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

The NM_001142807.4(ACOXL):​c.148A>G​(p.Thr50Ala) 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. 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: 3.26

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=0.3741653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACOXL	NM_001142807.4	c.148A>G	p.Thr50Ala	missense_variant	3/18	ENST00000439055.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOXL	ENST00000439055.6	c.148A>G	p.Thr50Ala	missense_variant	3/18	2	NM_001142807.4

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

Aug 01, 2022

The c.148A>G (p.T50A) alteration is located in exon 3 (coding exon 2) of the ACOXL gene. This alteration results from a A to G substitution at nucleotide position 148, causing the threonine (T) at amino acid position 50 to be replaced by an alanine (A). 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	0.12
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0039	T;.;.;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.038
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.63	T;T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Uncertain	0.54	D
MutationAssessor	Uncertain	2.1	M;M;M;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.4	N;N;N;D
REVEL	Uncertain	0.37
Sift	Benign	0.038	D;T;D;D
Sift4G	Uncertain	0.052	T;T;T;D
Polyphen		0.0060	B;.;.;.
Vest4		0.49
MutPred		0.33		Loss of ubiquitination at K53 (P = 0.1322);Loss of ubiquitination at K53 (P = 0.1322);Loss of ubiquitination at K53 (P = 0.1322);Loss of ubiquitination at K53 (P = 0.1322);
MVP		0.79
MPC		0.21
ClinPred		0.66	D
GERP RS		3.0
Varity_R		0.060
gMVP		0.32

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: rs887505142; hg19: chr2-111542381;