Variant 4-8375108-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003501.3(ACOX3):c.1698G>C(p.Thr566Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 1,554,806 control chromosomes in the GnomAD database, including 397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.029 ( 83 hom., cov: 33)

Exomes 𝑓: 0.018 ( 314 hom. )

Consequence

ACOX3
NM_003501.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -3.04

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 Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 4-8375108-C-G is Benign according to our data. Variant chr4-8375108-C-G is described in ClinVar as [Benign]. Clinvar id is 559047.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOX3	NM_003501.3 link	c.1698G>C	p.Thr566Thr	synonymous_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.1698G>C	p.Thr566Thr	synonymous_variant	15/18	1	NM_003501.3	ENSP00000348775.4	O15254-1
ACOX3	ENST00000503233.5 link	c.1698G>C	p.Thr566Thr	synonymous_variant	15/18	1		ENSP00000421625.1	O15254-1
ACOX3	ENST00000413009.6 link	c.1698G>C	p.Thr566Thr	synonymous_variant	15/17	1		ENSP00000413994.2	O15254-2
ACOX3	ENST00000510365.5 link	n.1410G>C		non_coding_transcript_exon_variant	13/13	5

Frequencies

GnomAD3 genomes

AF:

0.0291

AC:

4430

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0617

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.0305

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0151

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0187

AC:

2986

AN:

160044

Hom.:

AF XY:

0.0190

AC XY:

1616

AN XY:

85130

show subpopulations

Gnomad AFR exome

AF:

0.0657

Gnomad AMR exome

AF:

0.0112

Gnomad ASJ exome

AF:

0.0338

Gnomad EAS exome

AF:

0.0000835

Gnomad SAS exome

AF:

0.0184

Gnomad FIN exome

AF:

0.0123

Gnomad NFE exome

AF:

0.0174

Gnomad OTH exome

AF:

0.0238

GnomAD4 exome

AF:

0.0176

AC:

24715

AN:

1402466

Hom.:

314

Cov.:

AF XY:

0.0177

AC XY:

12244

AN XY:

691990

show subpopulations

Gnomad4 AFR exome

AF:

0.0645

Gnomad4 AMR exome

AF:

0.0134

Gnomad4 ASJ exome

AF:

0.0330

Gnomad4 EAS exome

AF:

0.0000546

Gnomad4 SAS exome

AF:

0.0184

Gnomad4 FIN exome

AF:

0.0113

Gnomad4 NFE exome

AF:

0.0165

Gnomad4 OTH exome

AF:

0.0216

GnomAD4 genome

AF:

0.0291

AC:

4440

AN:

152340

Hom.:

Cov.:

AF XY:

0.0282

AC XY:

2103

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0618

Gnomad4 AMR

AF:

0.0163

Gnomad4 ASJ

AF:

0.0305

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0147

Gnomad4 FIN

AF:

0.0103

Gnomad4 NFE

AF:

0.0186

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.0316

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Sep 27, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.018

DANN

Benign

0.67

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