ClinVar Genomic variation as it relates to human health
NM_000133.4(F9):c.1135C>T (p.Arg379Ter)
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000133.4(F9):c.1135C>T (p.Arg379Ter)
Variation ID: 10612 Accession: VCV000010612.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: Xq27.1 X: 139561820 (GRCh38) [ NCBI UCSC ] X: 138643979 (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 Apr 4, 2013 Feb 28, 2024 Jul 16, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000133.4:c.1135C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000124.1:p.Arg379Ter nonsense NM_001313913.2:c.1021C>T NP_001300842.1:p.Arg341Ter nonsense NC_000023.11:g.139561820C>T NC_000023.10:g.138643979C>T NG_007994.1:g.36085C>T LRG_556:g.36085C>T LRG_556t1:c.1135C>T LRG_556p1:p.Arg379Ter - Protein change
- R379*, R341*
- Other names
- F9, ARG333TER
- R333*
- Canonical SPDI
- NC_000023.11:139561819: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
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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F9 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
581 | 765 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Pathogenic (2) |
no assertion criteria provided
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Jun 1, 2019 | RCV000011358.3 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 2, 2018 | RCV001000157.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 16, 2023 | RCV001851791.6 |
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
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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
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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
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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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Pathogenic
(Oct 02, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001156643.1
First in ClinVar: Feb 10, 2020 Last updated: Feb 10, 2020 |
Comment:
The F9 c.1135C>T; p.Arg379Ter variant (rs137852258), also known as Arg333Ter, has been described in several individuals affected with severe hemophilia B (see link to F9 … (more)
The F9 c.1135C>T; p.Arg379Ter variant (rs137852258), also known as Arg333Ter, has been described in several individuals affected with severe hemophilia B (see link to F9 database and references therein). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant induces an early termination codon, other truncating variants have been identified occurring further into the C terminus, and at least two of these variants result in a stable mRNA (F9 database, Li 2013, Gitschier 1985). Therefore, this nonsense variant likely results in a truncated protein and is considered pathogenic. References: Link to F9 database: http://www.factorix.org/ Li T et al. The CDC Hemophilia B mutation project mutation list: a new online resource. Mol Genet Genomic Med. 2013 Nov;1(4):238-45. Gitschier J et al. Genetic mapping and diagnosis of haemophilia A achieved through a BclI polymorphism in the factor VIII gene. Nature. 1985 Apr 25-May 1;314(6013):738-40. (less)
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Pathogenic
(Jul 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Thrombophilia, X-linked, due to factor 9 defect
Hereditary factor IX deficiency disease
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002234982.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 28, 2024 |
Comment:
This premature translational stop signal has been observed in individuals with Hemophilia B (PMID: 1969838, 8091381, 22544209, 31026269). This sequence change creates a premature translational … (more)
This premature translational stop signal has been observed in individuals with Hemophilia B (PMID: 1969838, 8091381, 22544209, 31026269). This sequence change creates a premature translational stop signal (p.Arg379*) in the F9 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 83 amino acid(s) of the F9 protein. This variant is not present in population databases (gnomAD no frequency). This variant is also known as Arg333Gln. ClinVar contains an entry for this variant (Variation ID: 10612). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Aug 01, 1990)
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no assertion criteria provided
Method: literature only
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HEMOPHILIA B
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000031590.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
See Zhang et al. (1989). This mutation, due to a transition at a CpG dinucleotide, was found by Koeberl et al. (1990) in 2 patients … (more)
See Zhang et al. (1989). This mutation, due to a transition at a CpG dinucleotide, was found by Koeberl et al. (1990) in 2 patients with severe hemophilia B (306900). (less)
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Pathogenic
(Jun 01, 2019)
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no assertion criteria provided
Method: clinical testing
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Hereditary factor IX deficiency disease
Affected status: yes
Allele origin:
germline
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Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Accession: SCV001424897.1
First in ClinVar: Nov 19, 2020 Last updated: Nov 19, 2020 |
Number of individuals with the variant: 1
Sex: female
Ethnicity/Population group: Causasians
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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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Targeted re-sequencing of F8, F9 and VWF: Characterization of Ion Torrent data and clinical implications for mutation screening. | Manderstedt E | PloS one | 2019 | PMID: 31026269 |
Assessment of the F9 genotype-specific FIX inhibitor risks and characterisation of 10 novel severe F9 defects in the first molecular series of Argentinian patients with haemophilia B. | Radic CP | Thrombosis and haemostasis | 2013 | PMID: 23093250 |
Spectrum of F9 mutations in Chinese haemophilia B patients: identification of 20 novel mutations. | Yu T | Pathology | 2012 | PMID: 22544209 |
FIX mutation spectrum in haemophilia B patients from Jordan: identification of three novel mutations. | Awidi A | Haemophilia : the official journal of the World Federation of Hemophilia | 2011 | PMID: 20695909 |
Polymorphism in factor VII gene modifies phenotype of severe haemophilia. | Jayandharan GR | Haemophilia : the official journal of the World Federation of Hemophilia | 2009 | PMID: 19686262 |
Identification of mutations in the F9 gene including exon deletion by multiplex ligation-dependent probe amplification in 33 unrelated Korean patients with haemophilia B. | Kwon MJ | Haemophilia : the official journal of the World Federation of Hemophilia | 2008 | PMID: 18624698 |
Mutation analysis of haemophilia B in the Irish population: increased prevalence caused by founder effect. | Jenkins PV | Haemophilia : the official journal of the World Federation of Hemophilia | 2008 | PMID: 18479429 |
Allelic heterogeneity of molecular events in human coagulation factor IX in Asian Indians. Mutation in brief #965. Online. | Mahajan A | Human mutation | 2007 | PMID: 17397055 |
Molecular characterization of factor IX gene mutations in 53 patients with haemophilia B in India. | Jayandharan GR | Thrombosis and haemostasis | 2005 | PMID: 16270648 |
Molecular genotyping of the Italian cohort of patients with hemophilia B. | Belvini D | Haematologica | 2005 | PMID: 15921378 |
Molecular pathology of haemophilia B in Turkish patients: identification of a large deletion and 33 independent point mutations. | Onay UV | British journal of haematology | 2003 | PMID: 12588353 |
Haemophilia B mutations in Sweden: a population-based study of mutational heterogeneity. | Ljung R | British journal of haematology | 2001 | PMID: 11328285 |
Fast and efficient mutation detection method using multiplex PCR and cycle sequencing--application to haemophilia B. | Costa JM | Thrombosis and haemostasis | 2000 | PMID: 10739381 |
Molecular analysis of hemophilia B in Poland: 12 novel mutations of the factor IX gene. | Wulff K | Acta biochimica Polonica | 1999 | PMID: 10698280 |
Factor IX gene analysis in 70 unrelated patients with haemophilia B: description of 13 new mutations. | Attali O | Thrombosis and haemostasis | 1999 | PMID: 10595634 |
Ultrarapid mutation detection by multiplex, solid-phase chemical cleavage. | Rowley G | Genomics | 1995 | PMID: 8825645 |
Heteroduplex screening for molecular defects in factor IX genes from haemophilia B families. | Chen SH | British journal of haematology | 1995 | PMID: 7873393 |
First report on UK database of haemophilia B mutations and pedigrees. UK Haemophilia Centres. | Saad S | Thrombosis and haemostasis | 1994 | PMID: 8091381 |
Germline mutations in the factor IX gene: a comparison of the pattern in Caucasians and non-Caucasians. | Gostout B | Human molecular genetics | 1993 | PMID: 8499919 |
Genetic basis and carrier detection of hemophilia B of Chinese origin. | Lin SW | Thrombosis and haemostasis | 1993 | PMID: 8470048 |
Germ-line origins of mutation in families with hemophilia B: the sex ratio varies with the type of mutation. | Ketterling RP | American journal of human genetics | 1993 | PMID: 8434583 |
Recurrent mutations in the factor IX gene: founder effect or repeat de novo events. Investigation of the German haemophilia B population and review of de novo mutations. | Knobloch O | Human genetics | 1993 | PMID: 8365725 |
Single-strand conformation polymorphism (SSCP) analysis of the molecular pathology of hemophilia B. | David D | Human mutation | 1993 | PMID: 8257988 |
Twenty-four novel hemophilia B mutations revealed by rapid scanning of the whole factor IX gene in a French population sample. | Ghanem N | European journal of human genetics : EJHG | 1993 | PMID: 8055323 |
Factor IX mutations: rapid, direct screening methods for 20 new families with hemophilia B. | Thompson AR | Thrombosis research | 1992 | PMID: 1579901 |
CG dinucleotide transitions in the factor IX gene account for about half of the point mutations in hemophilia B patients: a Seattle series. | Chen SH | Human genetics | 1991 | PMID: 2066105 |
Missense mutations and evolutionary conservation of amino acids: evidence that many of the amino acids in factor IX function as "spacer" elements. | Bottema CD | American journal of human genetics | 1991 | PMID: 1680287 |
The pattern of factor IX germ-line mutation in Asians is similar to that of Caucasians. | Bottema CD | American journal of human genetics | 1990 | PMID: 2220823 |
Mutations causing hemophilia B: direct estimate of the underlying rates of spontaneous germ-line transitions, transversions, and deletions in a human gene. | Koeberl DD | American journal of human genetics | 1990 | PMID: 2198809 |
Abstracts of papers presented at a joint meeting of the British Society for Haemostasis and Thrombosis and Nederlandse Vereniging voor Trombose en Hemostase, Charing Cross and Westminster Medical School, London, 17-18 September 1990. | - | British journal of haematology | 1990 | PMID: 2093364 |
Recurrent nonsense mutations at arginine residues cause severe hemophilia B in unrelated hemophiliacs. | Koeberl DD | Human genetics | 1990 | PMID: 1969838 |
Zhang, M., Chen, S.-H., Thompson, A. R., Lovrien, E., Scott, C. R. CG dinucleotides are 'hot spots' in the factor IX gene for point mutations: evidence from the study of 25 families with defined mutations causing hemophilia B. (Abstract) Am. J. Hum. Genet. 45: A231, 1989. | - | - | - | - |
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Text-mined citations for rs137852258 ...
HelpRecord last updated Sep 29, 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.