SIAE M89V - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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Curation:
Currentness:

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SIAE M89V

(SIAE Met89Val)


You are viewing an old version of this page that was saved on June 16, 2010 at 6:25pm by Madeleine Ball.

Edited in this revision:

Short summary

This variant was reported to be associated with autoimmune disease when homozygous. Because multiple hypotheses are effectively tested, the significance of the case/control data is unclear. Assuming it is pathogenic, the small sample size (due to variant rarity) means that it is unclear to what extent the variant increases relative risk.

Variant evidence
Computational 1

Polyphen predicts “possibly damaging”. Surolia et al. find other variants in this gene associated with autoimmune disease.

Functional 2

Surolia et al. report that the protein product with this variant is catalytically active but is not secreted. This finding was reproduced in a pulse-chase experiment with 35S-methionine.

Case/Control 1

Surolia et al., see below.

See unpublished research (below).

Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pathogenic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

recessive

Summary of published research, and additional commentary

Surolia, I. et al. Nature advance online publication doi:10.1038/nature09115 (2010). — This paper implicates this polymorphism as potentially contributing to autoimmune diseases when homozygous. The variant was seen homozygously in 8 out of 923 cases and 0 out of 648 controls. Using two-tailed Fisher’s Exact, this is p = 0.024. However, because there are several other polymorphisms, multiple hypotheses were implicitly being tested and so we give this a case/control significance of 1 point (0.1 < p < 0.05). The overall allele frequency of the variant in controls is 0.049, they list four other variants with allele frequencies > 0.025.

They report that the protein product with this variant is catalytically active but is not secreted. This finding was reproduced in a pulse-chase experiment with 35S-methionine.

Allele frequency

  • C @ chr11:124530664: 4.0% (431/10758) in EVS
  • C @ chr11:124035873: 5.5% (7/128) in GET-Evidence
  • Frequency shown in summary reports: 4.0% (431/10758)

Publications
 

Genomes
 

hu43860C - CGI sample GS00253-DNA_A01_200_37
het C @ chr11:124530664

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
het C @ chr11:124530664

 

Other external references
 

    dbSNP
  • rs78778622
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.015 (benign)

Other in silico analyses
 

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 0

Edit history
 

Gene search

"GENE" or "GENE A123C":

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