VCV002138110.4 - ClinVar

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

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(4)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

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

Variation ID: 2138110 Accession: VCV002138110.4

Type and length

Microsatellite, 4 bp

Location

Cytogenetic: 17q25.1 17: 75948394-75948397 (GRCh38) [ NCBI UCSC ] 17: 73944475-73944478 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 8, 2023	Jan 25, 2025	Jan 15, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_004035.7:c.1789_1792del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_004026.2:p.Leu596_Thr597insTer	nonsense
NM_001185039.2:c.1675_1678del	NP_001171968.1:p.Leu558_Thr559insTer	nonsense
NM_007292.6:c.1789_1792del	NP_009223.2:p.Leu596_Thr597insTer	nonsense
NC_000017.11:g.75948394GAGT[1]
NC_000017.10:g.73944475GAGT[1]
NG_008190.1:g.35963ACTC[1]

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000017.11:75948393:GAGTGAGT:GAGT

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA8776655 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ACOX1		-	-	GRCh38 GRCh37	829	857

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Acyl-CoA oxidase deficiency	Pathogenic/Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Nov 18, 2023	RCV003041325.3
Acyl-CoA oxidase deficiency Mitchell syndrome	Pathogenic (1)	criteria provided, single submitter	Jan 15, 2024	RCV005019591.1
Mitchell syndrome	Likely pathogenic (1)	criteria provided, single submitter	May 18, 2022	RCV003475498.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely pathogenic (May 18, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Mitchell syndrome Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004211477.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023
Likely pathogenic (Nov 08, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Acyl-CoA oxidase deficiency Affected status: yes Allele origin: germline	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center Accession: SCV004244476.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024	Comment: PVS1, PM2
Pathogenic (Nov 18, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Acyl-CoA oxidase deficiency Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003442518.2 First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024	Publications: PubMed (2) PubMed: 8040306‚ 17458872 Comment: 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 … (more) 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. (less)
Pathogenic (Jan 15, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Acyl-CoA oxidase deficiency Mitchell syndrome Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Fulgent Genetics, Fulgent Genetics Accession: SCV005651946.1 First in ClinVar: Jan 25, 2025 Last updated: Jan 25, 2025

Comment:

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.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Clinical, biochemical, and mutational spectrum of peroxisomal acyl-coenzyme A oxidase deficiency.	Ferdinandusse S	Human mutation	2007	PMID: 17458872
Large deletion of the peroxisomal acyl-CoA oxidase gene in pseudoneonatal adrenoleukodystrophy.	Fournier B	The Journal of clinical investigation	1994	PMID: 8040306

Text-mined citations for this variant ...

Record last updated Feb 01, 2025

ClinVar Genomic variation as it relates to human health

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

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...