TXNDC3 I338T - GET-Evidence

Curation:
Currentness:

TXNDC3 I338T

(TXNDC3 Ile338Thr)


Short summary

Tentatively classified as benign, but predicted to be damaging and other variants in this gene are implicated in causing primary ciliary dyskinesia (situs inversus, chronic sinusitis, and bronchiectasis).

Variant evidence
Computational -1

Polyphen 2 predicts damaging effect

Functional -
Case/Control 1

Allele frequency implies the variant is not severely pathogenic, but more observations would help establish this as significant.

See unpublished research (below).

Familial -
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, Uncertain benign

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

Inheritance pattern

unknown

Summary of published research, and additional commentary

No known publications, found heterozygously in 4 out of 64 PGP + public genomes (allele frequency of 3.1%). This variant is predicted to be damaging by Polyphen 2 and other variants in this gene are associated with causing primary ciliary dyskinesia, presumably in a recessive manner. OMIM only reports a single case with mutations in this gene (compound heterozygous for L426X and an intronic/splicing mutation). This GeneReviews article gives an incidence of 1 in 16,000: http://www.ncbi.nlm.nih.gov/books/NBK1122/

To test whether our observations of this variant in random controls significantly contradicts a pathogenic hypothesis, we test this variant against a hypothetical pathogenic variant responsible for 10% of PCD cases with moderate (5%) penetrance (1 in 8,000 homozygous, 1 in 160,000 affected) — this hypothetical variant would have an allele frequency of 1.1%. The chances of seeing this variant in 4 out of 128 random alleles is p=0.056.

Allele frequency

  • C @ chr7:37923923: 3.8% (406/10752) in EVS
  • C @ chr7:37890447: 3.1% (4/128) in GET-Evidence
  • Frequency shown in summary reports: 3.8% (406/10752)

Publications
 

Genomes
 

 

hu43860C - CGI sample GS00253-DNA_A01_200_37
hom C @ chr7:37923923

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het C @ chr7:37923923

 

GS20502 - var-GS20502-1100-36-ASM
het C @ chr7:37890448

 

Other external references
 

    dbSNP
  • rs62001870
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    GeneTests
  • GeneTests records for the TXNDC3 gene
    Primary Ciliary Dyskinesia
    Primary Ciliary Dyskinesia 6: TXNDC3-Related Primary Ciliary Dys
    www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/TXNDC3
    PolyPhen-2
  • Score: 0.999 (probably damaging)
    Web search results (0 hits -- see all)

Other in silico analyses
 

  • NBLOSUM100 score = 3
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

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