Variant 4-8375053-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003501.3(ACOX3):c.1753C>T(p.Arg585Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000643 in 1,554,610 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

ACOX3
NM_003501.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23

Variant links:

Genes affected

ACOX3 (HGNC:121): (acyl-CoA oxidase 3, pristanoyl) Acyl-Coenzyme A oxidase 3 also know as pristanoyl -CoA oxidase (ACOX3)is involved in the desaturation of 2-methyl branched fatty acids in peroxisomes. Unlike the rat homolog, the human gene is expressed in very low amounts in liver such that its mRNA was undetectable by routine Northern-blot analysis or its product by immunoblotting or by enzyme activity measurements. However the human cDNA encoding a 700 amino acid protein with a peroxisomal targeting C-terminal tripeptide S-K-L was isolated and is thought to be expressed under special conditions such as specific developmental stages or in a tissue specific manner in tissues that have not yet been examined. [provided by RefSeq, Jul 2008]

ACOX3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
ACOX3	NM_003501.3 link	c.1753C>T	p.Arg585Trp	missense_variant	15/18	ENST00000356406.10	NP_003492.2	O15254-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ACOX3	ENST00000356406.10 link	c.1753C>T	p.Arg585Trp	missense_variant	15/18	1	NM_003501.3	ENSP00000348775.4	O15254-1
ACOX3	ENST00000503233.5 link	c.1753C>T	p.Arg585Trp	missense_variant	15/18	1		ENSP00000421625.1	O15254-1
ACOX3	ENST00000413009.6 link	c.1753C>T	p.Arg585Trp	missense_variant	15/17	1		ENSP00000413994.2	O15254-2
ACOX3	ENST00000510365.5 link	n.1465C>T		non_coding_transcript_exon_variant	13/13	5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000321

AC:

AN:

155684

Hom.:

AF XY:

0.0000241

AC XY:

AN XY:

82984

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000259

Gnomad SAS exome

AF:

0.0000434

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000428

AC:

AN:

1402262

Hom.:

Cov.:

AF XY:

0.00000578

AC XY:

AN XY:

691900

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000279

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000546

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.25e-7

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Bravo

AF:

0.0000113

ExAC

AF:

0.00000930

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

May 03, 2023

The c.1753C>T (p.R585W) alteration is located in exon 15 (coding exon 14) of the ACOX3 gene. This alteration results from a C to T substitution at nucleotide position 1753, causing the arginine (R) at amino acid position 585 to be replaced by a tryptophan (W). 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

0.15

BayesDel_addAF

Uncertain

0.054

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.53

D;.;D

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

.;D;D

M_CAP

Benign

0.034

MetaRNN

Uncertain

0.62

D;D;D

MetaSVM

Uncertain

-0.16

MutationAssessor

Uncertain

2.9

M;M;M

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.6

D;D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.50

MutPred

0.61

Loss of disorder (P = 0.0167);Loss of disorder (P = 0.0167);Loss of disorder (P = 0.0167);

MVP

0.63

MPC

0.50

ClinPred

0.84

GERP RS

4.3

Varity_R

0.28

gMVP

0.49

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