Variant 4-8371000-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003501.3(ACOX3):c.1897-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,613,676 control chromosomes in the GnomAD database, including 1,177 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.027 ( 69 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1108 hom. )

Consequence

ACOX3
NM_003501.3 splice_region, intron

Scores

Splicing: ADA: 0.00006976

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.122

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 4-8371000-G-A is Benign according to our data. Variant chr4-8371000-G-A is described in ClinVar as [Benign]. Clinvar id is 559045.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOX3	NM_003501.3 link	c.1897-6C>T		splice_region_variant, intron_variant		ENST00000356406.10	NP_003492.2	O15254-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOX3	ENST00000356406.10 link	c.1897-6C>T		splice_region_variant, intron_variant		1	NM_003501.3	ENSP00000348775.4		O15254-1

Frequencies

GnomAD3 genomes

AF:

0.0267

AC:

4064

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00639

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.0328

Gnomad ASJ

AF:

0.0484

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0767

Gnomad FIN

AF:

0.0233

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0343

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0319

AC:

8000

AN:

251028

Hom.:

222

AF XY:

0.0356

AC XY:

4829

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.00548

Gnomad AMR exome

AF:

0.0207

Gnomad ASJ exome

AF:

0.0488

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0787

Gnomad FIN exome

AF:

0.0204

Gnomad NFE exome

AF:

0.0320

Gnomad OTH exome

AF:

0.0351

GnomAD4 exome

AF:

0.0346

AC:

50604

AN:

1461378

Hom.:

1108

Cov.:

AF XY:

0.0361

AC XY:

26279

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.00550

Gnomad4 AMR exome

AF:

0.0219

Gnomad4 ASJ exome

AF:

0.0506

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0814

Gnomad4 FIN exome

AF:

0.0209

Gnomad4 NFE exome

AF:

0.0338

Gnomad4 OTH exome

AF:

0.0356

GnomAD4 genome

AF:

0.0267

AC:

4062

AN:

152298

Hom.:

Cov.:

AF XY:

0.0266

AC XY:

1981

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00638

Gnomad4 AMR

AF:

0.0327

Gnomad4 ASJ

AF:

0.0484

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0765

Gnomad4 FIN

AF:

0.0233

Gnomad4 NFE

AF:

0.0343

Gnomad4 OTH

AF:

0.0284

Alfa

AF:

0.0302

Hom.:

Bravo

AF:

0.0252

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0375

EpiControl

AF:

0.0392

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	May 10, 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

-0.67

CADD

Benign

7.8

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000070

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.050

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