ClinVar Genomic variation as it relates to human health
NM_001079866.2(BCS1L):c.217C>T (p.Arg73Cys)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic(1); Uncertain significance(3); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001079866.2(BCS1L):c.217C>T (p.Arg73Cys)
Variation ID: 554974 Accession: VCV000554974.32
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q35 2: 218661204 (GRCh38) [ NCBI UCSC ] 2: 219525927 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Aug 5, 2018 Apr 15, 2024 Jan 29, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001079866.2:c.217C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001073335.1:p.Arg73Cys missense NM_001257342.2:c.217C>T NP_001244271.1:p.Arg73Cys missense NM_001257343.2:c.217C>T NP_001244272.1:p.Arg73Cys missense NM_001257344.2:c.217C>T NP_001244273.1:p.Arg73Cys missense NM_001318836.2:c.-40-202C>T intron variant NM_001320717.2:c.217C>T NP_001307646.1:p.Arg73Cys missense NM_001371443.1:c.217C>T NP_001358372.1:p.Arg73Cys missense NM_001371444.1:c.217C>T NP_001358373.1:p.Arg73Cys missense NM_001371446.1:c.217C>T NP_001358375.1:p.Arg73Cys missense NM_001371447.1:c.217C>T NP_001358376.1:p.Arg73Cys missense NM_001371448.1:c.217C>T NP_001358377.1:p.Arg73Cys missense NM_001371449.1:c.217C>T NP_001358378.1:p.Arg73Cys missense NM_001371450.1:c.217C>T NP_001358379.1:p.Arg73Cys missense NM_001371451.1:c.-40-202C>T intron variant NM_001371452.1:c.-41-555C>T intron variant NM_001371453.1:c.-260C>T 5 prime UTR NM_001371454.1:c.-260C>T 5 prime UTR NM_001371455.1:c.-260C>T 5 prime UTR NM_001371456.1:c.-260C>T 5 prime UTR NM_001374085.1:c.217C>T NP_001361014.1:p.Arg73Cys missense NM_001374086.1:c.-260C>T 5 prime UTR NM_004328.5:c.217C>T NP_004319.1:p.Arg73Cys missense NR_163955.1:n.1229C>T non-coding transcript variant NC_000002.12:g.218661204C>T NC_000002.11:g.219525927C>T NG_008018.1:g.6549C>T NG_033099.1:g.3337G>A LRG_539:g.6549C>T LRG_539t1:c.217C>T LRG_539p1:p.Arg73Cys - Protein change
- R73C
- Other names
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- Canonical SPDI
- NC_000002.12:218661203:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00006
Exome Aggregation Consortium (ExAC) 0.00008
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
The Genome Aggregation Database (gnomAD), exomes 0.00016
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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BCS1L | - | - |
GRCh38 GRCh37 |
484 | 519 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (1) |
criteria provided, single submitter
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Nov 9, 2017 | RCV000670706.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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May 22, 2017 | RCV000778591.5 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jan 29, 2024 | RCV001171821.25 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(Nov 09, 2017)
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criteria provided, single submitter
Method: clinical testing
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GRACILE syndrome
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000795597.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Uncertain significance
(May 22, 2017)
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criteria provided, single submitter
Method: clinical testing
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Mitochondrial complex III deficiency nuclear type 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000914898.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The BCS1L c.217C>T (p.Arg73Cys) variant has been reported in two studies in the same individual with mitochondrial respiratory chain complex III deficiency in a compound … (more)
The BCS1L c.217C>T (p.Arg73Cys) variant has been reported in two studies in the same individual with mitochondrial respiratory chain complex III deficiency in a compound heterozygous state with another missense variant (Fernandez-Vizarra et al. 2007; Invernizzi et al. 2012). The p.Arg73Cys variant was absent from 210 control alleles, but is reported at a frequency of 0.00315 in the Ashkenazi Jewish population of the Genome Aggregation Database. The Arg73 residue is conserved across multiple species. Patient fibroblasts showed 30% residual enzyme activity and 50% maximum respiration rate compared to wild type (Invernizzi et al. 2012). Growth complementation studies in yeast showed that the p.Arg73Cys variant alone was insufficient to cause a growth defect, but in the presence of the other missense variant from the compound heterozygous patient, growth was significantly reduced compared to wild type. A similar result was obtained looking at the mitochondrial cytochrome profile and respiration activity (Fernandez-Vizarra et al. 2007; Invernizzi et al. 2012). The evidence for this variant is limited. The p.Arg73Cys variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for mitochondrial respiratory chain complex III deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Uncertain significance
(Oct 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV004170563.1
First in ClinVar: Nov 25, 2023 Last updated: Nov 25, 2023 |
Comment:
Identified with a second variant in a patient with BCS1L-related mitochondrial complex III deficiency in the published literature (PMID: 17403714); In silico analysis supports that … (more)
Identified with a second variant in a patient with BCS1L-related mitochondrial complex III deficiency in the published literature (PMID: 17403714); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22310368, 23168492, 30582773, 17403714) (less)
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Likely benign
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001689654.4
First in ClinVar: Jun 08, 2021 Last updated: Feb 14, 2024 |
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Pathogenic
(Mar 01, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001334690.19
First in ClinVar: Jun 08, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Microscale oxygraphy reveals OXPHOS impairment in MRC mutant cells. | Invernizzi F | Mitochondrion | 2012 | PMID: 22310368 |
Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy. | Fernandez-Vizarra E | Human molecular genetics | 2007 | PMID: 17403714 |
Text-mined citations for rs140812286 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.