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NM_000133.4(F9):c.1062T>A (p.Ser354Arg) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 20, 2021
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:
RCV001930794.5

Allele description

NM_000133.4(F9):c.1062T>A (p.Ser354Arg)

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.1062T>A (p.Ser354Arg)
HGVS:
  • NC_000023.11:g.139561747T>A
  • NG_007994.1:g.36012T>A
  • NM_000133.4:c.1062T>AMANE SELECT
  • NM_001313913.2:c.948T>A
  • NP_000124.1:p.Ser354Arg
  • NP_001300842.1:p.Ser316Arg
  • LRG_556:g.36012T>A
  • NC_000023.10:g.138643906T>A
Protein change:
S316R
Links:
dbSNP: rs2148367882
NCBI 1000 Genomes Browser:
rs2148367882
Molecular consequence:
  • NM_000133.4:c.1062T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001313913.2:c.948T>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002189217Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 20, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Hemophilia B is a quasi-quantitative condition with certain mutations showing phenotypic plasticity.

Chavali S, Ghosh S, Bharadwaj D.

Genomics. 2009 Dec;94(6):433-7. doi: 10.1016/j.ygeno.2009.08.005. Epub 2009 Aug 19.

PubMed [citation]
PMID:
19699296

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, SCV002189217.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ser354 amino acid residue in F9. Other variant(s) that disrupt this residue have been observed in individuals with F9-related conditions (PMID: 19699296), which suggests that this may be a clinically significant amino acid residue. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt F9 protein function. This missense change has been observed in individual(s) with clinical features of hemophilia B (PMID: 7937052, Invitae). These variants are also known as T31045G (308, S->R) and A31043C (308S->R). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with arginine at codon 354 of the F9 protein (p.Ser354Arg). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and arginine.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 5, 2024