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NM_000118.3(ENG):c.7C>T (p.Arg3Cys)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(2);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
6 (Most recent: Sep 1, 2021)
Last evaluated:
Oct 9, 2020
Accession:
VCV000374952.14
Variation ID:
374952
Description:
single nucleotide variant
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NM_000118.3(ENG):c.7C>T (p.Arg3Cys)

Allele ID
361866
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
9q34.11
Genomic location
9: 127854349 (GRCh38) GRCh38 UCSC
9: 130616628 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000009.11:g.130616628G>A
NC_000009.12:g.127854349G>A
NG_009551.1:g.5420C>T
... more HGVS
Protein change
R3C
Other names
-
Canonical SPDI
NC_000009.12:127854348:G:A
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00029
Exome Aggregation Consortium (ExAC) 0.00055
The Genome Aggregation Database (gnomAD) 0.00022
Trans-Omics for Precision Medicine (TOPMed) 0.00028
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00031
Links
ClinGen: CA5253268
dbSNP: rs139334561
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely benign 3 criteria provided, multiple submitters, no conflicts Jan 12, 2018 RCV000415646.7
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Aug 28, 2020 RCV000488039.5
Uncertain significance 1 criteria provided, single submitter Oct 9, 2020 RCV001034662.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
ENG Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
590 883

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Oct 09, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary hemorrhagic telangiectasia
Allele origin: germline
Invitae
Accession: SCV000546111.6
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (4)
Comment:
This sequence change replaces arginine with cysteine at codon 3 of the ENG protein (p.Arg3Cys). The arginine residue is weakly conserved and there is a … (more)
Uncertain significance
(Nov 01, 2016)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
CeGaT Praxis fuer Humangenetik Tuebingen
Accession: SCV000575593.12
Submitted: (Jul 04, 2021)
Evidence details
Likely benign
(Jan 12, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary hemorrhagic telangiectasia type 1
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV001332251.1
Submitted: (Feb 20, 2020)
Evidence details
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
Likely benign
(Jan 01, 2018)
criteria provided, single submitter
Method: research
Hereditary hemorrhagic telangiectasia type 1
Allele origin: unknown
NIHR Bioresource Rare Diseases, University of Cambridge
Accession: SCV001439459.1
Submitted: (May 21, 2020)
Evidence details
Publications
PubMed (1)
Comment:
BS1 +BP2
Uncertain significance
(Aug 28, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001816344.1
Submitted: (Sep 01, 2021)
Evidence details
Comment:
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: 15312062, … (more)
Uncertain significance
(Jan 27, 2016)
no assertion criteria provided
Method: clinical testing
Hereditary hemorrhagic telangiectasia type 1
Allele origin: germline
Knight Diagnostic Laboratories, Oregon Health and Sciences University
Study: CSER-NextGen
Accession: SCV000493740.1
Submitted: (Aug 10, 2016)
Evidence details

Functional evidence

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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 this variant

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Title Author Journal Year Link
Mutational and phenotypic characterization of hereditary hemorrhagic telangiectasia. Shovlin CL Blood 2020 PMID: 32573726
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation. Kobayashi Y Genome medicine 2017 PMID: 28166811
Functional analysis of endoglin mutations from hereditary hemorrhagic telangiectasia type 1 patients reveals different mechanisms for endoglin loss of function. Mallet C Human molecular genetics 2015 PMID: 25312062
The modified CAMDEX informant interview is a valid and reliable tool for use in the diagnosis of dementia in adults with Down's syndrome. Ball SL Journal of intellectual disability research : JIDR 2004 PMID: 15312062

Text-mined citations for rs139334561...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 07, 2021