PCCA I475V - GET-Evidence

Curation:
Currentness:

PCCA I475V

(PCCA Ile475Val)


Short summary

Reported as a polymorphism, tentatively presumed benign.

Variant evidence
Computational 1

BLOSUM100 indicates Ile to Val is not disruptive

Functional -
Case/Control 2

If Richard et al.‘s allele frequency data is correct, this would contradict a pathogenic effect. However, it deviates significantly from observations in GET-Evidence data.

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

 

Allele frequency

  • G @ chr13:100962156: 3.8% (406/10758) in EVS
  • G @ chr13:99760156: 0.8% (1/126) in GET-Evidence
  • Frequency shown in summary reports: 3.8% (406/10758)

Publications
 

Richard E, Desviat LR, Pérez B, Pérez-Cerdá C, Ugarte M. Genetic heterogeneity in propionic acidemia patients with alpha-subunit defects. Identification of five novel mutations, one of them causing instability of the protein. Biochim Biophys Acta. 1999 Mar 30;1453(3):351-8. PubMed PMID: 10101253.

The authors report this variant and seem to imply it’s a polymorphism. It’s seen homozygously in two out of 24 patients with propionic acidemia, but also seen in seven random chromosomes in a screen of 39 control individuals. Of the patients, one had another potential explanatory homozygous variant, the other no other was found by their sequencing. An allele frequency of 9% in controls is highly contradicting the rarity of this genetic disease.

Counting alleles, case+: 2, case-: 22, control+: 7, control-: 71 — no statistically significant difference.

The allele frequency reported in their controls differs significantly from that in GET-Evidence data (1 / 128), potentially reflecting a higher concentration of the variant in the ethnic background in their study, although the authors do not mention the ethnicity/origin of their controls.

Genomes
 

hu04FD18 - CGI sample GS00253-DNA_F01_200_37
het G @ chr13:100962156

 

hu92C40A - CGI sample GS01175-DNA_G03 from PGP sample 92527586
het G @ chr13:100962156

 

 

Other external references
 

    dbSNP
  • rs35719359
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    Web search results (1 hit -- see all)
  • Supplementary Table xls.1
    Administrator B**a***=***£***h*J*\I08*X*@*ì*"*******1* É*ÿ**Arial1* É*ÿ**Arial1 ... rs16957356*PCCA NM_000282 NP_000273*S557L3propionyl Coenzyme A carboxylase, alpha ...
    icr.ac.uk/research/research_sections/.../2843.xls

Other in silico analyses
 

  • NBLOSUM100 score = –4
  • GET-Evidence autoscore = 2

Edit history
 

Gene search

"GENE" or "GENE A123C":

Log in