Variant 2-110805366-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001142807.4(ACOXL):c.724G>T(p.Val242Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

ACOXL
NM_001142807.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.510

Variant links:

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]

ACOXL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13734731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACOXL	NM_001142807.4 linkuse as main transcript	c.724G>T	p.Val242Leu	missense_variant	9/18	ENST00000439055.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOXL	ENST00000439055.6 linkuse as main transcript	c.724G>T	p.Val242Leu	missense_variant	9/18	2	NM_001142807.4		Q9NUZ1-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251474

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000658

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 09, 2022

The c.724G>T (p.V242L) alteration is located in exon 9 (coding exon 8) of the ACOXL gene. This alteration results from a G to T substitution at nucleotide position 724, causing the valine (V) at amino acid position 242 to be replaced by a leucine (L). 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

0.29

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.25

T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.66

T;T;T;T

M_CAP

Benign

0.060

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-0.36

MutationAssessor

Benign

0.045

N;N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.3

N;N;N;N

REVEL

Benign

0.21

Sift

Benign

0.91

T;T;T;T

Sift4G

Benign

0.31

T;T;T;T

Polyphen

0.0090

B;.;.;.

Vest4

0.37

MutPred

0.75

Loss of MoRF binding (P = 0.1031);Loss of MoRF binding (P = 0.1031);Loss of MoRF binding (P = 0.1031);.;

MVP

0.50

MPC

0.18

ClinPred

0.020

GERP RS

1.9

Varity_R

0.087

gMVP

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over