Submissions for variant NM_000133.4(F9):c.484C>T (p.Arg162Ter)

dbSNP: rs137852272

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001000188	SCV001156683	pathogenic	not specified	2018-12-11	criteria provided, single submitter	clinical testing	The F9 c.484C>T; p.Arg162Ter variant (rs137852272), also known as Arg116Ter, has been described in multiple individuals affected with severe hemophilia B (see link to F9 database and references therein, Lin 2018). It contains and entry in ClinVar (Variation ID: 10640) and 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 and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered pathogenic. REFERENCES Link to F9 database: http://www.factorix.org/ Lin X et al. Establishing a comprehensive genetic diagnosis strategy for hemophilia B and its application in Chinese population. Int J Lab Hematol. 2018 Apr;40(2):215-228.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003764553	SCV004571546	pathogenic	Hereditary factor IX deficiency disease; Thrombophilia, X-linked, due to factor 9 defect	2023-11-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg162*) in the F9 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in F9 are known to be pathogenic (PMID: 20301668). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hemophilia B (PMID: 32875744). This variant is also known as 17,761C>T 116R>stop. ClinVar contains an entry for this variant (Variation ID: 10640). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
OMIM	RCV000011386	SCV000031618	pathogenic	Hereditary factor IX deficiency disease	1990-07-01	no assertion criteria provided	literature only
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	RCV000011386	SCV001424898	pathogenic	Hereditary factor IX deficiency disease	2019-06-01	no assertion criteria provided	clinical testing