NM_000466.3(PEX1):c.721del (p.Ser241fs) AND Zellweger spectrum disorders

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 3, 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:: RCV001066600.6

Allele description [Variation Report for NM_000466.3(PEX1):c.721del (p.Ser241fs)]

NM_000466.3(PEX1):c.721del (p.Ser241fs)

Gene:

PEX1:peroxisomal biogenesis factor 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7q21.2

Genomic location:

Preferred name:

NM_000466.3(PEX1):c.721del (p.Ser241fs)

HGVS:

NC_000007.14:g.92517794del
NG_008341.2:g.15738del
NM_000466.3:c.721delMANE SELECT
NM_001282677.2:c.721del
NM_001282678.2:c.97del
NP_000457.1:p.Ser241fs
NP_001269606.1:p.Ser241fs
NP_001269607.1:p.Ser33fs
NC_000007.13:g.92147108del
NG_008341.1:g.15738del
NM_000466.2:c.721del

Protein change:

S241fs

Links:

dbSNP: rs894289737

NCBI 1000 Genomes Browser:

rs894289737

Molecular consequence:

NM_000466.3:c.721del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282677.2:c.721del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282678.2:c.97del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001231615	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 3, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21031596, 26387595, 31831025, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001231615

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 3, 2023)

germline

clinical testing

PubMed (4)
[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

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

Heimler Syndrome Is Caused by Hypomorphic Mutations in the Peroxisome-Biogenesis Genes PEX1 and PEX6.

Ratbi I, Falkenberg KD, Sommen M, Al-Sheqaih N, Guaoua S, Vandeweyer G, Urquhart JE, Chandler KE, Williams SG, Roberts NA, El Alloussi M, Black GC, Ferdinandusse S, Ramdi H, Heimler A, Fryer A, Lynch SA, Cooper N, Ong KR, Smith CE, Inglehearn CF, Mighell AJ, et al.

Am J Hum Genet. 2015 Oct 1;97(4):535-45. doi: 10.1016/j.ajhg.2015.08.011. Epub 2015 Sep 17.

PubMed [citation]

PMID:: 26387595
PMCID:: PMC4596894

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001231615.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Ser241Glnfs*2) 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: 21031596, 26387595, 31831025). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PEX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 591770). 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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