The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_000133.4(F9):c.224G>A (p.Arg75Gln)

CA255318

10573 (ClinVar)

Gene: F9
Condition: hemophilia B
Inheritance Mode: X-linked inheritance
UUID: 178efdc9-7922-4e7d-8479-352a42eedd02
Approved on: 2024-10-11
Published on: 2025-01-07

HGVS expressions

NM_000133.4:c.224G>A
NM_000133.4(F9):c.224G>A (p.Arg75Gln)
NC_000023.11:g.139537145G>A
CM000685.2:g.139537145G>A
NC_000023.10:g.138619304G>A
CM000685.1:g.138619304G>A
NC_000023.9:g.138446970G>A
NG_007994.1:g.11410G>A
ENST00000218099.7:c.224G>A
ENST00000218099.6:c.224G>A
ENST00000394090.2:c.224G>A
ENST00000479617.2:n.231G>A
NM_000133.3:c.224G>A
NM_001313913.1:c.224G>A
NM_001313913.2:c.224G>A
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Pathogenic

Met criteria codes 4
PP4_Moderate PM2_Supporting PS4_Very Strong PP3
Not Met criteria codes 1
PM1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Coagulation Factor Deficiency Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for F9 Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Coagulation Factor Deficiency VCEP
NM_000133.4(F9):c.224G>A (p.Arg75Gln) missense variant has a REVEL score of 0.904, which meets criteria for PP3. This variant is absent from males in population databases (gnomAD v2.1.1/gnomAD v3). Approximately 24 patients are reported in the literature with mild hemophilia B and this variant, meeting F9 phenotype criteria for PS4_Very strong (PMID: 31064749, PMID: 2066105, PMID: 8314564, PMID: 29296726, PMID: 27213901, PMID: 2773937). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel for F9: PS4_Very strong, PP4_Moderate, PP3, PM2_supporting.
Met criteria codes
PP4_Moderate
Counting one of the MLOF probands
PM2_Supporting
This variant is absent from males in population databases (gnomAD v2.1.1/gnomAD v3).
PS4_Very Strong
Greater than 16 individuals reported in the literature with mild hemophilia B. The criterion is met at the very strong evidence level.
PP3
REVEL score is 0.904, which is below the 0.6 cutoff.
Not Met criteria codes
PM1
Variant is not within exons 3, 4 or 5.
Curation History
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