NM_004035.7(ACOX1):c.1789_1792del (p.Leu596_Thr597insTer) AND Acyl-CoA oxidase deficiency

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Nov 18, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003041325.3

Allele description [Variation Report for NM_004035.7(ACOX1):c.1789_1792del (p.Leu596_Thr597insTer)]

NM_004035.7(ACOX1):c.1789_1792del (p.Leu596_Thr597insTer)

Gene:

ACOX1:acyl-CoA oxidase 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

17q25.1

Genomic location:

Preferred name:

NM_004035.7(ACOX1):c.1789_1792del (p.Leu596_Thr597insTer)

HGVS:

NC_000017.11:g.75948394GAGT[1]
NG_008190.1:g.35963ACTC[1]
NM_001185039.2:c.1675_1678del
NM_004035.7:c.1789_1792delMANE SELECT
NM_007292.6:c.1789_1792del
NP_001171968.1:p.Leu558_Thr559insTer
NP_004026.2:p.Leu596_Thr597insTer
NP_009223.2:p.Leu596_Thr597insTer
NC_000017.10:g.73944475GAGT[1]
NC_000017.10:g.73944475_73944478del

Molecular consequence:

NM_001185039.2:c.1675_1678del - nonsense - [Sequence Ontology: SO:0001587]
NM_004035.7:c.1789_1792del - nonsense - [Sequence Ontology: SO:0001587]
NM_007292.6:c.1789_1792del - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Acyl-CoA oxidase deficiency
Synonyms:: STRAIGHT-CHAIN ACYL-CoA OXIDASE DEFICIENCY; Pseudoneonatal adrenoleukodystrophy; Pseudoadrenoleukodystrophy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009919; MedGen: C1849678; Orphanet: 2971; OMIM: 264470

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003442518	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 18, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 8040306, 17458872, 28492532
SCV004244476	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 8, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003442518

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 18, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004244476

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 8, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Large deletion of the peroxisomal acyl-CoA oxidase gene in pseudoneonatal adrenoleukodystrophy.

Fournier B, Saudubray JM, Benichou B, Lyonnet S, Munnich A, Clevers H, Poll-The BT.

J Clin Invest. 1994 Aug;94(2):526-31.

PubMed [citation]

PMID:: 8040306
PMCID:: PMC296126

Clinical, biochemical, and mutational spectrum of peroxisomal acyl-coenzyme A oxidase deficiency.

Ferdinandusse S, Denis S, Hogenhout EM, Koster J, van Roermund CW, IJlst L, Moser AB, Wanders RJ, Waterham HR.

Hum Mutat. 2007 Sep;28(9):904-12.

PubMed [citation]

PMID:: 17458872

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003442518.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Thr597*) in the ACOX1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACOX1 are known to be pathogenic (PMID: 8040306, 17458872). This variant is present in population databases (rs769644289, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with peroxisomal acyl-CoA oxidase deficiency (PMID: 17458872). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV004244476.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

PVS1, PM2

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 1, 2025

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