NM_000466.3(PEX1):c.3450T>A (p.Cys1150Ter) AND Zellweger spectrum disorders

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 17, 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:: RCV001382765.7

Allele description [Variation Report for NM_000466.3(PEX1):c.3450T>A (p.Cys1150Ter)]

NM_000466.3(PEX1):c.3450T>A (p.Cys1150Ter)

Genes:

GATAD1:GATA zinc finger domain containing 1 [Gene - OMIM - HGNC]
PEX1:peroxisomal biogenesis factor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q21.2

Genomic location:

Preferred name:

NM_000466.3(PEX1):c.3450T>A (p.Cys1150Ter)

HGVS:

NC_000007.14:g.92489900A>T
NG_008341.2:g.43632T>A
NM_000466.3:c.3450T>AMANE SELECT
NM_001282677.2:c.3279T>A
NM_001282678.2:c.2826T>A
NP_000457.1:p.Cys1150Ter
NP_001269606.1:p.Cys1093Ter
NP_001269607.1:p.Cys942Ter
NC_000007.13:g.92119214A>T

Protein change:

C1093*

Links:

dbSNP: rs1459743428

NCBI 1000 Genomes Browser:

rs1459743428

Molecular consequence:

NM_000466.3:c.3450T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001282677.2:c.3279T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001282678.2:c.2826T>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Zellweger spectrum disorders (ZS)
Synonyms:: Zellweger syndrome; Zellweger Spectrum Disorder; Zellweger Spectrum
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
SCV001581669	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 17, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 9398847, 16086329, 16141001, 21031596, 26387595, 31831025, 31628608, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001581669

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 17, 2023)

germline

clinical testing

PubMed (8)
[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

Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders.

Reuber BE, Germain-Lee E, Collins CS, Morrell JC, Ameritunga R, Moser HW, Valle D, Gould SJ.

Nat Genet. 1997 Dec;17(4):445-8.

PubMed [citation]

PMID:: 9398847

PEX1 mutations in the Zellweger spectrum of the peroxisome biogenesis disorders.

Crane DI, Maxwell MA, Paton BC.

Hum Mutat. 2005 Sep;26(3):167-75. Review.

PubMed [citation]

PMID:: 16086329

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001581669.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change creates a premature translational stop signal (p.Cys1150*) in the PEX1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PEX1 are known to be pathogenic (PMID: 9398847, 16086329, 16141001, 21031596, 26387595, 31831025). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Zellweger syndrome (PMID: 31628608). ClinVar contains an entry for this variant (Variation ID: 1070573). 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

Last Updated: Sep 29, 2024

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