NM_001351132.2(PEX5):c.826C>T (p.Arg276Ter) AND Zellweger spectrum disorders

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 23, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV004017960.1

Allele description [Variation Report for NM_001351132.2(PEX5):c.826C>T (p.Arg276Ter)]

NM_001351132.2(PEX5):c.826C>T (p.Arg276Ter)

Gene:

PEX5:peroxisomal biogenesis factor 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p13.31

Genomic location:

Preferred name:

NM_001351132.2(PEX5):c.826C>T (p.Arg276Ter)

HGVS:

NC_000012.12:g.7202684C>T
NG_008448.1:g.18522C>T
NM_000319.5:c.826C>T
NM_001131023.2:c.871C>T
NM_001131024.2:c.715C>T
NM_001131025.2:c.826C>T
NM_001131026.2:c.826C>T
NM_001300789.3:c.826C>T
NM_001351124.3:c.715C>T
NM_001351126.2:c.715C>T
NM_001351127.2:c.715C>T
NM_001351128.2:c.715C>T
NM_001351130.3:c.715C>T
NM_001351131.2:c.826C>T
NM_001351132.2:c.826C>TMANE SELECT
NM_001351133.2:c.826C>T
NM_001351134.2:c.826C>T
NM_001351135.3:c.760C>T
NM_001351136.2:c.826C>T
NM_001351137.3:c.715C>T
NM_001351138.2:c.760C>T
NM_001351139.2:c.715C>T
NM_001351140.2:c.715C>T
NM_001374645.1:c.715C>T
NM_001374646.1:c.715C>T
NM_001374647.2:c.826C>T
NM_001374648.2:c.715C>T
NM_001374649.2:c.715C>T
NP_000310.2:p.Arg276Ter
NP_001124495.1:p.Arg291Ter
NP_001124496.1:p.Arg239Ter
NP_001124497.1:p.Arg276Ter
NP_001124498.1:p.Arg276Ter
NP_001287718.2:p.Arg276Ter
NP_001338053.1:p.Arg239Ter
NP_001338055.1:p.Arg239Ter
NP_001338056.1:p.Arg239Ter
NP_001338057.1:p.Arg239Ter
NP_001338059.1:p.Arg239Ter
NP_001338060.1:p.Arg276Ter
NP_001338061.1:p.Arg276Ter
NP_001338062.1:p.Arg276Ter
NP_001338063.1:p.Arg276Ter
NP_001338064.2:p.Arg254Ter
NP_001338065.1:p.Arg276Ter
NP_001338066.2:p.Arg239Ter
NP_001338067.1:p.Arg254Ter
NP_001338068.1:p.Arg239Ter
NP_001338069.1:p.Arg239Ter
NP_001361574.1:p.Arg239Ter
NP_001361575.1:p.Arg239Ter
NP_001361576.1:p.Arg276Ter
NP_001361577.1:p.Arg239Ter
NP_001361578.1:p.Arg239Ter
NC_000012.11:g.7355280C>T

Protein change:

R239*

Links:

dbSNP: rs267608194

Molecular consequence:

NM_000319.5:c.826C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001131023.2:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001131024.2:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001131025.2:c.826C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001131026.2:c.826C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001300789.3:c.826C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351124.3:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351126.2:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351127.2:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351128.2:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351130.3:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351131.2:c.826C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351132.2:c.826C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351133.2:c.826C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351134.2:c.826C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351135.3:c.760C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351136.2:c.826C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351137.3:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351138.2:c.760C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351139.2:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001351140.2:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001374645.1:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001374646.1:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001374647.2:c.826C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001374648.2:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001374649.2:c.715C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Zellweger spectrum disorders (ZS)
Synonyms:: Zellweger syndrome; Zellweger Spectrum Disorder; Zellweger Spectrum; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0019609; MedGen: C0043459; Orphanet: 912

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004847354	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Pathogenic (Oct 23, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18712838, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004847354

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Pathogenic
(Oct 23, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Genotype-phenotype correlation in PEX5-deficient peroxisome biogenesis defective cell lines.

Ebberink MS, Mooyer PA, Koster J, Dekker CJ, Eyskens FJ, Dionisi-Vici C, Clayton PT, Barth PG, Wanders RJ, Waterham HR.

Hum Mutat. 2009 Jan;30(1):93-8. doi: 10.1002/humu.20833.

PubMed [citation]

PMID:: 18712838

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847354.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.Arg276X variant in PEX5 has been identified in the homozygous state in 1 individual with clinical features of Zellweger spectrum disorder (Ebberink 2009 PMID: 18712838). This variant has also been reported by other clinical laboratories in ClinVar (Variation ID 2137295) and was absent from large population studies (gnomAD, v.3.1.2).This nonsense variant leads to a premature termination codon at position 276, which is predicted to lead to a truncated or absent protein. Biallelic loss of function of the PEX5 gene is an established disease mechanism in autosomal recessive Zellweger spectrum disorder. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Zellweger spectrum disorder. ACMG/AMP Criteria applied: PVS1, PM2_Supporting.

#	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

Last Updated: Apr 12, 2026

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Relating variation to medicine