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NM_000133.4(F9):c.142A>G (p.Asn48Asp) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 22, 2023
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:
RCV003783784.1

Allele description

NM_000133.4(F9):c.142A>G (p.Asn48Asp)

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.142A>G (p.Asn48Asp)
HGVS:
  • NC_000023.11:g.139537063A>G
  • NG_007994.1:g.11328A>G
  • NM_000133.4:c.142A>GMANE SELECT
  • NM_001313913.2:c.142A>G
  • NP_000124.1:p.Asn48Asp
  • NP_000124.1:p.Asn48Asp
  • NP_001300842.1:p.Asn48Asp
  • LRG_556t1:c.142A>G
  • LRG_556:g.11328A>G
  • LRG_556p1:p.Asn48Asp
  • NC_000023.10:g.138619222A>G
  • NM_000133.3:c.142A>G
Protein change:
N48D
Molecular consequence:
  • NM_000133.4:c.142A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001313913.2:c.142A>G - 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
SCV004571468Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Mar 22, 2023) 		germlineclinical testing

PubMed (5)
[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

Fast and efficient mutation detection method using multiplex PCR and cycle sequencing--application to haemophilia B.

Costa JM, Ernault P, Vidaud D, Vidaud M, Meyer D, Lavergne JM.

Thromb Haemost. 2000 Feb;83(2):244-7.

PubMed [citation]
PMID:
10739381

Analysis of F9 point mutations and their correlation to severity of haemophilia B disease.

Hamasaki-Katagiri N, Salari R, Simhadri VL, Tseng SC, Needlman E, Edwards NC, Sauna ZE, Grigoryan V, Komar AA, Przytycka TM, Kimchi-Sarfaty C.

Haemophilia. 2012 Nov;18(6):933-40. doi: 10.1111/j.1365-2516.2012.02848.x. Epub 2012 May 29.

PubMed [citation]
PMID:
22639855
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV004571468.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This variant disrupts the p.Asn48 amino acid residue in F9. Other variant(s) that disrupt this residue have been observed in individuals with F9-related conditions (PMID: 7937052, 10739381, 22639855), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change does not substantially affect F9 function (PMID: 8463288). 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 variant is also known as A6379G; FIX/ND+2. This missense change has been observed in individuals with hemophilia B (PMID: 7937052; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 48 of the F9 protein (p.Asn48Asp).

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

Last Updated: Mar 5, 2024