NM_004328.4(BCS1L):c.166C>T (p.Arg56Ter) AND GRACILE syndrome

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jul 22, 2016)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000576565.2

Allele description [Variation Report for NM_004328.4(BCS1L):c.166C>T (p.Arg56Ter)]

NM_004328.4(BCS1L):c.166C>T (p.Arg56Ter)

Gene:
BCS1L:BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q35
Genomic location:
Preferred name:
NM_004328.4(BCS1L):c.166C>T (p.Arg56Ter)
Other names:
p.R56*:CGA>TGA
HGVS:
  • NC_000002.12:g.218661153C>T
  • NG_008018.1:g.6498C>T
  • NM_001257342.1:c.166C>T
  • NM_001257344.1:c.166C>T
  • NM_001318836.1:c.-40-253C>T
  • NM_004328.4:c.166C>T
  • NP_001244271.1:p.Arg56Ter
  • NP_001244273.1:p.Arg56Ter
  • NP_004319.1:p.Arg56Ter
  • LRG_539t1:c.166C>T
  • LRG_539t2:c.166C>T
  • LRG_539:g.6498C>T
  • LRG_539p1:p.Arg56Ter
  • LRG_539p2:p.Arg56Ter
  • NC_000002.11:g.219525876C>T
Protein change:
R56*; ARG56TER
Links:
OMIM: 603647.0007; dbSNP: rs121908576
NCBI 1000 Genomes Browser:
rs121908576
Molecular consequence:
  • NM_001318836.1:c.-40-253C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_004328.4:c.166C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
GRACILE syndrome (FLNMS)
Identifiers:
MedGen: C1864002; Orphanet: 53693; OMIM: 603358

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000678020Counsylcriteria provided, single submitter
Likely pathogenic
(Oct 9, 2015)
unknownclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV000698303Integrated Genetics/Laboratory Corporation of Americacriteria provided, single submitter
Pathogenic
(Jul 22, 2016)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Clinical and diagnostic characteristics of complex III deficiency due to mutations in the BCS1L gene.

De Meirleir L, Seneca S, Damis E, Sepulchre B, Hoorens A, Gerlo E, GarcĂ­a Silva MT, Hernandez EM, Lissens W, Van Coster R.

Am J Med Genet A. 2003 Aug 30;121A(2):126-31.

PubMed [citation]
PMID:
12910490

BCS1L gene mutation presenting with GRACILE-like syndrome and complex III deficiency.

Lynn AM, King RI, Mackay RJ, Florkowski CM, Wilson CJ.

Ann Clin Biochem. 2012 Mar;49(Pt 2):201-3. doi: 10.1258/acb.2011.011180. Epub 2012 Jan 25.

PubMed [citation]
PMID:
22277166
See all PubMed Citations (4)

Details of each submission

From Counsyl, SCV000678020.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Integrated Genetics/Laboratory Corporation of America, SCV000698303.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

Variant summary: The BCS1L c.166C>T (p.Arg56X) variant results in a premature termination codon, predicted to cause a truncated or absent BCS1L protein due to nonsense mediated decay (NMD), which are commonly known mechanisms for disease. The variant is predicted to truncate N-terminal, P-loop and ATPase domains. Truncations downstream of this position (e.g. p.R186* and p.R291*, etc.) have been have been reported in patients with BCS1L-linked phenotypes in literature. Functional study shows that this variant drastically reduces the expression of mRNA (Gil-Borlado_2009). This variant was found in 23/122068 control chromosomes at a frequency of 0.0001884, which does not exceed the estimated maximal expected allele frequency of a pathogenic BCS1L variant (0.0025). This variant is found in several families/patients with complex III deficiency in compound heterozygous with other missense or promoter mutations. Multiple clinical diagnostic laboratories/reputable databases have classified this variant as pathogenic. Taken together, this variant is classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 30, 2019

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