Variant chr2-110841387-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001142807.4(ACOXL):c.770C>G(p.Ala257Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ACOXL
NM_001142807.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.88

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACOXL	NM_001142807.4 linkuse as main transcript	c.770C>G	p.Ala257Gly	missense_variant	10/18	ENST00000439055.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOXL	ENST00000439055.6 linkuse as main transcript	c.770C>G	p.Ala257Gly	missense_variant	10/18	2	NM_001142807.4		Q9NUZ1-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248566

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134308

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457372

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725046

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Dec 17, 2023

The c.770C>G (p.A257G) alteration is located in exon 10 (coding exon 9) of the ACOXL gene. This alteration results from a C to G substitution at nucleotide position 770, causing the alanine (A) at amino acid position 257 to be replaced by a glycine (G). 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

-0.0077

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;.;.;.

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Benign

0.048

MetaRNN

Pathogenic

0.88

D;D;D;D

MetaSVM

Benign

-0.37

MutationAssessor

Uncertain

2.4

M;M;M;.

MutationTaster

Benign

0.82

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.4

D;D;D;D

REVEL

Uncertain

0.55

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

0.074

T;D;D;D

Polyphen

0.98

D;.;.;.

Vest4

0.51

MutPred

0.81

Loss of stability (P = 0.0774);Loss of stability (P = 0.0774);Loss of stability (P = 0.0774);.;

MVP

0.81

MPC

0.71

ClinPred

0.96

GERP RS

4.3

Varity_R

0.59

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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