chr3-58505214-G-A

Position:

• chr3-58505214-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP6

The NM_003500.4(ACOX2):​c.*10C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ACOX2 NM_003500.4 3_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.06

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 3-58505214-G-A is Benign according to our data. Variant chr3-58505214-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3052899.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOX2	NM_003500.4	c.*10C>T		3_prime_UTR_variant	15/15	ENST00000302819.10	NP_003491.1
ACOX2	XM_047449042.1	c.*10C>T		3_prime_UTR_variant	15/15		XP_047304998.1
ACOX2	XM_005265505.2	c.*10C>T		3_prime_UTR_variant	15/15		XP_005265562.1
ACOX2	XM_006713340.4	c.*10C>T		3_prime_UTR_variant	14/14		XP_006713403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOX2	ENST00000302819	c.*10C>T		3_prime_UTR_variant	15/15	1	NM_003500.4	ENSP00000307697.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000799 AC: 2 AN: 250378 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135258

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000661

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1458628 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 725686

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: 0.0000467

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ACOX2-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 14, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs769731964; hg19: chr3-58490941;