Variant chr3-58517249-C-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_003500.4(ACOX2):c.1807G>A(p.Asp603Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000021 ( 0 hom. )

Consequence

ACOX2
NM_003500.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.02

Variant links:

Genes affected

ACOX2 (HGNC:120): (acyl-CoA oxidase 2) The product of this gene belongs to the acyl-CoA oxidase family. It encodes the branched-chain acyl-CoA oxidase which is involved in the degradation of long branched fatty acids and bile acid intermediates in peroxisomes. Deficiency of this enzyme results in the accumulation of branched fatty acids and bile acid intermediates, and may lead to Zellweger syndrome, severe cognitive disability, and death in children. [provided by RefSeq, Mar 2009]

ACOX2 links:

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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=0.22322404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ACOX2	NM_003500.4 linkuse as main transcript	c.1807G>A	p.Asp603Asn	missense_variant	13/15	ENST00000302819.10
ACOX2	XM_047449042.1 linkuse as main transcript	c.2005G>A	p.Asp669Asn	missense_variant	13/15
ACOX2	XM_005265505.2 linkuse as main transcript	c.1807G>A	p.Asp603Asn	missense_variant	13/15
ACOX2	XM_006713340.4 linkuse as main transcript	c.1513G>A	p.Asp505Asn	missense_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOX2	ENST00000302819.10 linkuse as main transcript	c.1807G>A	p.Asp603Asn	missense_variant	13/15	1	NM_003500.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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 02, 2023

The c.1807G>A (p.D603N) alteration is located in exon 13 (coding exon 12) of the ACOX2 gene. This alteration results from a G to A substitution at nucleotide position 1807, causing the aspartic acid (D) at amino acid position 603 to be replaced by an asparagine (N). 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

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.060

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.072

Sift

Benign

0.21

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.24

.;B

Vest4

0.31

MutPred

0.46

.;Gain of helix (P = 0.132);

MVP

0.48

MPC

0.30

ClinPred

0.85

GERP RS

4.9

Varity_R

0.12

gMVP

0.34

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