NM_000133.4(F9):c.364G>A (p.Gly122Arg) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 8, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001327375.6

Allele description

NM_000133.4(F9):c.364G>A (p.Gly122Arg)

Gene:

F9:coagulation factor IX [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq27.1

Genomic location:

Preferred name:

NM_000133.4(F9):c.364G>A (p.Gly122Arg)

HGVS:

NC_000023.11:g.139541162G>A
NG_007994.1:g.15427G>A
NM_000133.4:c.364G>AMANE SELECT
NM_001313913.2:c.277+3776G>A
NP_000124.1:p.Gly122Arg
LRG_556:g.15427G>A
NC_000023.10:g.138623321G>A

Protein change:

G122R

Links:

dbSNP: rs770120402

NCBI 1000 Genomes Browser:

rs770120402

Molecular consequence:

NM_001313913.2:c.277+3776G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000133.4:c.364G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary factor IX deficiency disease (HEMB)
Synonyms:: F9 DEFICIENCY; PLASMA THROMBOPLASTIN COMPONENT DEFICIENCY; Hemophilia B; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010604; MeSH: D002836; MedGen: C0008533; Orphanet: 98879; OMIM: 306900

Name:: Thrombophilia, X-linked, due to factor 9 defect
Synonyms:: Thrombophilia, X-linked, due to factor IX defect
Identifiers:: MONDO: MONDO:0010432; MedGen: C2749016; OMIM: 300807

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001518450	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 8, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 8594556, 7937052, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001518450

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 8, 2020)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Haemophilia B (sixth edition): a database of point mutations and short additions and deletions.

Giannelli F, Green PM, Sommer SS, Poon MC, Ludwig M, Schwaab R, Reitsma PH, Goossens M, Yoshioka A, Brownlee GG.

Nucleic Acids Res. 1996 Jan 1;24(1):103-18.

PubMed [citation]

PMID:: 8594556
PMCID:: PMC145614

Haemophilia B: database of point mutations and short additions and deletions, fifth edition, 1994.

Giannelli F, Green PM, Sommer SS, Lillicrap DP, Ludwig M, Schwaab R, Reitsma PH, Goossens M, Yoshioka A, Brownlee GG.

Nucleic Acids Res. 1994 Sep;22(17):3534-46.

PubMed [citation]

PMID:: 7937052
PMCID:: PMC308314

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001518450.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces glycine with arginine at codon 122 of the F9 protein (p.Gly122Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with F9-related conditions (PMID: 8594556). This variant is also known as G10478A in the literature. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Gly122 amino acid residue in F9. Other variant(s) that disrupt this residue have been observed in individuals with F9-related conditions (PMID: 7937052), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 5, 2024

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