NM_000466.3(PEX1):c.1A>T (p.Met1Leu) AND Zellweger syndrome

Clinical significance:Pathogenic (Last evaluated: Feb 2, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001384497.1

Allele description [Variation Report for NM_000466.3(PEX1):c.1A>T (p.Met1Leu)]

NM_000466.3(PEX1):c.1A>T (p.Met1Leu)

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.1A>T (p.Met1Leu)
HGVS:
  • NC_000007.14:g.92528435T>A
  • NG_008341.1:g.5097A>T
  • NG_008341.2:g.5097A>T
  • NM_000466.3:c.1A>TMANE SELECT
  • NM_001282677.2:c.1A>T
  • NM_001282678.2:c.-659A>T
  • NP_000457.1:p.Met1Leu
  • NP_001269606.1:p.Met1Leu
  • NC_000007.13:g.92157749T>A
  • NM_000466.2:c.1A>T
Protein change:
M1L
Links:
dbSNP: rs1057517501
NCBI 1000 Genomes Browser:
rs1057517501
Molecular consequence:
  • NM_001282678.2:c.-659A>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000466.3:c.1A>T - initiatior codon variant - [Sequence Ontology: SO:0001582]
  • NM_001282677.2:c.1A>T - initiatior codon variant - [Sequence Ontology: SO:0001582]
  • NM_000466.3:c.1A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282677.2:c.1A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Zellweger syndrome (ZS)
Identifiers:
MONDO: MONDO:0019609; MedGen: C0043459; Orphanet: 912

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001584007Invitaecriteria provided, single submitter
Pathogenic
(Feb 2, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

Genetic and clinical aspects of Zellweger spectrum patients with PEX1 mutations.

Rosewich H, Ohlenbusch A, Gärtner J.

J Med Genet. 2005 Sep;42(9):e58.

PubMed [citation]
PMID:
16141001
PMCID:
PMC1736134
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001584007.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change affects the initiator methionine of the PEX1 mRNA. The next in-frame methionine is located at codon 209. This variant is not present in population databases (ExAC no frequency). Disruption of the initiator codon has been observed in individual(s) with Zellweger spectrum disorder (PMID: 21031596). ClinVar contains an entry for this variant (Variation ID: 371744). This variant disrupts the initiator methionine in PEX1. If translation initiates from the next in-frame methionine, the PEX1 protein would no longer include the region containing the p.Val92 amino acid residue. Other variant(s) that disrupt this residue have been observed in individuals with PEX1-related conditions (PMID: 16141001), which suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2021

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