NM_000466.3(PEX1):c.1239+1G>T AND Zellweger spectrum disorders

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 31, 2024
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:: RCV001376605.7

Allele description [Variation Report for NM_000466.3(PEX1):c.1239+1G>T]

NM_000466.3(PEX1):c.1239+1G>T

Gene:

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.1239+1G>T

HGVS:

NC_000007.14:g.92517275C>A
NG_008341.2:g.16257G>T
NM_000466.3:c.1239+1G>TMANE SELECT
NM_001282677.2:c.1239+1G>T
NM_001282678.2:c.615+1G>T
NC_000007.13:g.92146589C>A
NM_000466.2:c.1239+1G>T

Nucleotide change:

IVS5, G-T, +1

Links:

OMIM: 602136.0008; dbSNP: rs756876301

NCBI 1000 Genomes Browser:

rs756876301

Molecular consequence:

NM_000466.3:c.1239+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001282677.2:c.1239+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001282678.2:c.615+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV000754535	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 31, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16199547, 21031596, 31831025, 19105186, 26387595, 28492532
SCV002076916	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 12, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000754535

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 31, 2024)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV002076916

Natera, Inc.

no assertion criteria provided

Pathogenic
(Sep 12, 2020)

germline

clinical testing

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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder.

Ebberink MS, Mooijer PA, Gootjes J, Koster J, Wanders RJ, Waterham HR.

Hum Mutat. 2011 Jan;32(1):59-69. doi: 10.1002/humu.21388.

PubMed [citation]

PMID:: 21031596

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000754535.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change affects a donor splice site in intron 5 of the PEX1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PEX1 are known to be pathogenic (PMID: 21031596, 26387595, 31831025). This variant is present in population databases (rs756876301, gnomAD 0.006%). Disruption of this splice site has been observed in individuals with peroxisomal biogenesis disorder (PMID: 19105186, 26387595). ClinVar contains an entry for this variant (Variation ID: 217430). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 Natera, Inc., SCV002076916.1

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

#	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: Nov 24, 2024

ClinVar

Relating variation to medicine