CBLC H405Y - GET-Evidence

Curation:
Currentness:

CBLC H405Y

(CBLC His405Tyr)


Short summary

Probably benign.

Variant evidence
Computational

Polyphen 2 predicts damaging effect, but BLOSUM100 predicts a His to Tyr substitution is not very disruptive.

Functional -
Case/Control 3

Frequency in HapMap, 1000 Genomes data, and PGP + public genomes supports no highly loss of function effect

See Lerner-Ellis JP et al. 2009 (19370762).

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

Polyphen 2 predicts a damaging effect; other damaging variants in this gene are associated with causing cobalamin c deficiency (complementation group C). Although it has not been reported upon as a polymorphism, the allele frequency of this variant is at odds with the rarity of this disease, and so we evaluate it as benign.

Allele frequency

  • T @ chr19:45296806: 3.7% (403/10758) in EVS
  • T @ chr19:49988645: 1.6% (2/124) in GET-Evidence
  • Frequency shown in summary reports: 3.7% (403/10758)

Publications
 

Lerner-Ellis JP, Anastasio N, Liu J, Coelho D, Suormala T, Stucki M, Loewy AD, Gurd S, Grundberg E, Morel CF, Watkins D, Baumgartner MR, Pastinen T, Rosenblatt DS, Fowler B. Spectrum of mutations in MMACHC, allelic expression, and evidence for genotype-phenotype correlations. Hum Mutat. 2009 Jul;30(7):1072-81. PubMed PMID: 19370762.

This variant is not mentioned in a list of CBLC mutations in patients reported on to date, at the time of publication.

Genomes
 

hu8229AE - CGI sample GS01173-DNA_A07 from PGP sample 96240009
het T @ chr19:45296806

 

huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het T @ chr19:45296806

 

GS06994 - var-GS06994-1100-36-ASM
het T @ chr19:49988646

 

Other external references
 

    dbSNP
  • rs3208856
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.958 (probably damaging)
    Web search results (1 hit -- see all)
  • Supplementary Table xls.1
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    icr.ac.uk/research/research_sections/.../2843.xls

Other in silico analyses
 

  • NBLOSUM100 score = –1
  • GET-Evidence autoscore = 5

Edit history
 

Gene search

"GENE" or "GENE A123C":

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