Evidence Repository
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 label mismatch: F9 vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • Despite there being a valid 'cspec' property in the messages there's a discrepancy in message contents and CSPEC data: * Message Gene: F9 CSPEC Genes: [ 'F8' ] * Message MONDOs: MONDO:0010604 CSPEC MONDO: [ 'MONDO:0010602' ]
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000133.4(F9):c.277G>A (p.Asp93Asn)

CA414436678

994410 (ClinVar)

Gene: F9 (HGNC:2158)
Condition: hemophilia B (MONDO:0010604)
Inheritance Mode: X-linked inheritance
UUID: ee4724ea-b5b0-4913-ac8e-dc8baa922b48
Approved on: 2025-05-02
Published on: 2025-05-02

HGVS expressions

NM_000133.4(F9):c.277G>A (p.Asp93Asn)
NM_000133.4:c.277G>A
NC_000023.11:g.139537386G>A
CM000685.2:g.139537386G>A
NC_000023.10:g.138619545G>A
CM000685.1:g.138619545G>A
NC_000023.9:g.138447211G>A
NG_007994.1:g.11651G>A
ENST00000218099.7:c.277G>A
ENST00000218099.6:c.277G>A
ENST00000394090.2:c.277G>A
ENST00000479617.2:n.241+231G>A
NM_000133.3:c.277G>A
NM_001313913.1:c.277G>A
NM_001313913.2:c.277G>A
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Pathogenic

Met criteria codes 3
PS4_Very Strong PP3 PM2_Supporting
Not Met criteria codes 2
PM1 PM5

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 F8 Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Coagulation Factor Deficiency VCEP
The NM_000133.4(F9):c.277G>A (p.Asp93Asn) variant is completely absent from gnomAD v2.1.1 and v3.1.2 meeting PM2_Supporting. At least 8 individuals with moderate-severe hemophilia B are found in the literature (PMIDs: 29296726, 11013449, 8091381, 22103590, 10698280, 2198809, 24656159) meeting criteria for PS4_Very strong. This missense variant has a REVEL score of 0.754 (>0.6), and the nucleotide is the last in exon 3 which SpliceAI predicts results in the loss of the splice donor of intron 3 (delta score of 0.93) meeting PP3. 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, PP3, PM2_Supporting.
Met criteria codes
PS4_Very Strong
At least 8 individuals with moderate-severe hemophilia B are found in the literature meeting criteria for PS4. All known cases were used for PS4 to maximize use at very strong (8 points).
PP3
The c.277G>A (p.Asp93Asn) missense variant has a REVEL score of 0.754 (>0.6). The nucleotide is the last in exon 3 and SpliceAI predicts that this variant results in the loss of the splice donor of intron 3 (delta score of 0.93).
PM2_Supporting
The c.277G>A (p.Asp93Asn) variant is completely absent from gnomAD v2.1.1 and v3.1.2.
Not Met criteria codes
PM1
The variant occurs in the last nucleotide of exon 3; however, this variant is predicted to cause a splicing defect, so this code is not applied.
PM5
Four variants at the same residue, Asp93His, Asp93Gly, Asp93Val, and Asp93Glu have been reported; however, this variant is suspected to cause a splicing defect so these additional variants were not evaluated.
Curation History
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