3-58505304-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_003500.4(ACOX2):c.1984-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000671 in 1,604,078 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00069 (1 hom.)
• Consequence: ACOX2 NM_003500.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.166

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-58505304-C-T is Benign according to our data. Variant chr3-58505304-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1988980.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACOX2	NM_003500.4	c.1984-18G>A		intron_variant		ENST00000302819.10
ACOX2	XM_005265505.2	c.1984-18G>A		intron_variant
ACOX2	XM_006713340.4	c.1690-18G>A		intron_variant
ACOX2	XM_047449042.1	c.2182-18G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOX2	ENST00000302819.10	c.1984-18G>A		intron_variant		1	NM_003500.4	P1

Frequencies

GnomAD3 genomes AF: 0.000467 AC: 71 AN: 152080 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000390 AC: 97 AN: 248720 Hom.: 1 AF XY: 0.000431 AC XY: 58 AN XY: 134434

Gnomad AFR exome AF: 0.000432

Gnomad AMR exome AF: 0.0000296

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000337

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.000699

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000693 AC: 1006 AN: 1451880 Hom.: 1 Cov.: 28 AF XY: 0.000657 AC XY: 475 AN XY: 722674

Gnomad4 AFR exome AF: 0.000421

Gnomad4 AMR exome AF: 0.0000905

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.000319

Gnomad4 NFE exome AF: 0.000846

Gnomad4 OTH exome AF: 0.000600

GnomAD4 genome AF: 0.000466 AC: 71 AN: 152198 Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32 AN XY: 74412

Gnomad4 AFR AF: 0.000482

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000342 Hom.: 0

Bravo AF: 0.000450

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 17, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.9
Dann	Benign	0.61

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: rs200767808; hg19: chr3-58491031;