PEX1 I696M - GET-Evidence

Curation:
Currentness:

PEX1 I696M

(PEX1 Ile696Met)


Short summary

Reported as a mutation causing peroxisome biogenesis disorder in a single patient, presumably in a recessive manner.

Variant evidence
Computational -1

Polyphen 2 predicts benign effect

Functional -
Case/Control

No controls reported, when using GET-Evidence as controls findings do not appear to be statistically significant.

See Walter C et al. 2001 (11389485).

Familial -
 
Clinical importance
Severity 5

Severe disorders of peroxisomes

Treatability 1
Penetrance 5

Presumed high penetrance

 

Impact

High clinical importance, Uncertain pathogenic

(The "high clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

recessive

Summary of published research, and additional commentary

 

Allele frequency

  • C @ chr7:92132493: 2.7% (291/10756) in EVS
  • C @ chr7:91970428: 1.6% (2/128) in GET-Evidence
  • Frequency shown in summary reports: 2.7% (291/10756)

Publications
 

Walter C, Gootjes J, Mooijer PA, Portsteffen H, Klein C, Waterham HR, Barth PG, Epplen JT, Kunau WH, Wanders RJ, Dodt G. Disorders of peroxisome biogenesis due to mutations in PEX1: phenotypes and PEX1 protein levels. Am J Hum Genet. 2001 Jul;69(1):35-48. Epub 2001 Jun 1. PubMed PMID: 11389485; PubMed Central PMCID: PMC1226046.

This variant was reported as a novel pathogenic finding in one patent (patient 8) in a screen of 22 cell lines from patients with peroxisome biogenesis disorders. It is unclear whether the authors are reporting a homozygote or heterozygote (and presumed compound heterozygote, although no other causal mutation in PEX1 is reported here for this patient). Controls are not mentioned.

Using GET-Evidence allele frequency information as a control and assuming this variant was only seen heterozygously, this observation is not statistically significant.

Genomes
 

 

hu604D39 - CGI sample GS00253-DNA_B02_200_37
het C @ chr7:92132493

 

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
het C @ chr7:92132493

 

 

Other external references
 

    dbSNP
  • rs35996821
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0 (benign)
    Web search results (2 hits -- see all)
  • g777g (32 Search Results)
    Two polymorphisms have been identified in the PEX1 gene, G777G and a 16 bp insertion ... Frequencyb c.2088A>G p.I696M. 0.03 c.2331C>A p.G777G. 0.84. PEX1 c.3762T>C p.A1254A ...
    teenwag.com/s?q=g777g
  • Disorders of Peroxisome Biogenesis Due to Mutations in PEX1 ...
    Approximately 65% of the patients with PBD harbor mutations in PEX1. ... indicates a newly identiļ¬ed HsPEX1 allele in patient 8, which results in I696M. ...
    sciencedirect.com/science?_ob=MImg&...&ie=/sdarticle.pdf

Other in silico analyses
 

  • NBLOSUM100 score = –1
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

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