ACAD8 S171C - GET-Evidence

Curation:
Currentness:

ACAD8 S171C

(ACAD8 Ser171Cys)


Short summary

This variant (a.k.a S149C) was found as a compound heterozygote (with M130T) in a male newborn of European descent with isobutyryl-CoA dehydrogenase deficiency (identified by newborn screening). Lack of controls means that significance cannot be established and allele frequency cannot be estimated. Oglesbee et al. comment that IBD-deficiency may be relatively benign, most cases identified by newborn screening have remained asymptomatic, but Ferreira et al. report a symptomatic individual homozygous for this variant.

Variant evidence
Computational 1

Gene associated with this disease

See Oglesbee D et al. 2007 (17304052).

Functional

Patient’s cell line showed expected biochemical properties, but this is not a variant-specific test (another causal variant may exist)

See Oglesbee D et al. 2007 (17304052).

Case/Control

Insufficient data to determine.

See unpublished research (below).

Familial -
 
Clinical importance
Severity 2

Many individuals are not symptomatic.

See Oglesbee D et al. 2007 (17304052).

Treatability 3

Treatment is available if needed.

See Oglesbee D et al. 2007 (17304052).

Penetrance

Unknown if this has any impact on disease frequency

 

Impact

Low clinical importance, Uncertain pathogenic

(The "low 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

This enzymatic condition is likely benign.

Total cases/controls case+ case– control+ control– p-value odds ratio
Isobutyryl-CoA Dehydrogenase Deficiency
1 12 0 0 - -

 

Allele frequency

  • G @ chr11:134128923: 1.8% (197/10758) in EVS
  • G @ chr11:133634132: 2.3% (3/128) in GET-Evidence
  • Frequency shown in summary reports: 1.8% (197/10758)

Publications
 

Oglesbee D, He M, Majumder N, Vockley J, Ahmad A, Angle B, Burton B, Charrow J, Ensenauer R, Ficicioglu CH, Keppen LD, Marsden D, Tortorelli S, Hahn SH, Matern D. Development of a newborn screening follow-up algorithm for the diagnosis of isobutyryl-CoA dehydrogenase deficiency. Genet Med. 2007 Feb;9(2):108-16. PubMed PMID: 17304052.

In a screen of 13 isobutyryl-CoA dehydrogenase deficiency patients identified through newborn screening, this variant (aka S149C) was found as a compound heterozygote (with M130T) in a male of European descent. The M130T variant was also found in 2 other patients. The cell line from this patient confirmed the biochemical phenotype. Normal controls were not reported, and the authors conclude that the condition is probably benign.

Cases/controls case+ case– control+ control– p-value odds ratio
Isobutyryl-CoA Dehydrogenase Deficiency
1 12 - - - -

 

Abstracts of the Annual Symposium of the Society for the Study of Inborn Errors of Metabolism. Lisboa, Portugal. September, 2-5, 2008. J Inherit Metab Dis. 2008 Aug;31 Suppl 1:1-192. PubMed PMID: 18677552.

Found in a homozygously in a four-year-old girl in Portugal with feeding difficulties, systolic murmur, hypotonia, developmental delay, a systolic murmur and slight enlargement of the left ventricle. Metabolic investigation showed elevated isobutyryl/butyrylcarnatine, and mutation analysis of the ACAD8 gene showed homozygosity for the variant S171C (512C>G). This symptomatic case was diagnosed before the generalized implementation of newborn screening in Portugal.

Genomes
 

hu43860C - CGI sample GS00253-DNA_A01_200_37
het G @ chr11:134128923

 

huA0E089 - CGI sample GS01175-DNA_B04 from PGP sample 88590671
het G @ chr11:134128923

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
het G @ chr11:134128923

 

huFAF983 - CGI sample GS01175-DNA_F02 from PGP sample 95788191
het G @ chr11:134128923

 

GS06985 - var-GS06985-1100-36-ASM
het G @ chr11:133634133

 

Other external references
 

    dbSNP
  • rs113488591
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0.985 (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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