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
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_000133.4(F9):c.1048T>G (p.Ser350Ala)

CA10529866

1685803 (ClinVar)

Gene: F9 (HGNC:2158)
Condition: hemophilia B (MONDO:0010604)
Inheritance Mode: X-linked inheritance
UUID: 69e8c03b-45bb-450e-9a31-e5f2bc4bc746
Approved on: 2025-04-04
Published on: 2025-04-04

HGVS expressions

NM_000133.4(F9):c.1048T>G (p.Ser350Ala)
NM_000133.4:c.1048T>G
NC_000023.11:g.139561733T>G
CM000685.2:g.139561733T>G
NC_000023.10:g.138643892T>G
CM000685.1:g.138643892T>G
NC_000023.9:g.138471558T>G
NG_007994.1:g.35998T>G
ENST00000218099.7:c.1048T>G
ENST00000643157.1:n.1715T>G
ENST00000218099.6:c.1048T>G
ENST00000394090.2:c.934T>G
NM_000133.3:c.1048T>G
NM_001313913.1:c.934T>G
NM_001313913.2:c.934T>G
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Benign

Met criteria codes 2
BP4 BA1
Not Met criteria codes 1
PS4

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
The c.1048T>G variant in F9 is a missense variant predicted to cause substitution of Serine by Alanine at amino acid 350 (p.Ser350Ala). This variant has been reported in 1 proband meeting phenotypic criteria for mild Hemophilia B. However, PS4_Supporting cannot be applied because more than 3 males in gnomAD v2.1.1 are reported with this variant, as per CFD VCEP specifications (PMID: 23492913). The highest population minor allele frequency in gnomAD v2.1.1 is 0.0006494 (9/13858 alleles) in the East Asian population, which is higher than the ClinGen Coagulation Factor Deficiency VCEP threshold (>=0.0000556) for BA1, and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.291, which is below the threshold (<= 0.3) and the splice site predictor Splice AI indicated that the variant has no impact on splicing (score = 0,0,0,0), evidence that does not predict a damaging effect on F9 function (BP4). In summary, this variant meets the criteria to be classified as Benign for Hemophilia B based on the ACMG/AMP criteria applied, as specified by the ClinGen Coagulation Factor Deficiency VCEP (version 1.0.0, released 10/5/2023): BA1, BP4.
Met criteria codes
BP4
The computational predictor REVEL gives a score of 0.291, which is below the threshold (<= 0.3) and the splice site predictor Splice AI indicated that the variant has no impact on splicing (score = 0,0,0,0), evidence that does not predict a damaging effect on F9 function (BP4).
BA1
The highest population minor allele frequency in gnomAD v2.1.1 is 0.0006494 (9/13858 alleles) in the East Asian population, which is higher than the ClinGen Coagulation Factor Deficiency VCEP threshold (>=0.0000556) for BA1, and therefore meets this criterion (BA1). The highest MAF in gnomAD v4.1.0 is 0.0008 (27/33749) in the East Asian population.
Not Met criteria codes
PS4
This variant has been reported in 1 proband meeting phenotypic criteria for mild Hemophilia B. However, PS4_Supporting cannot be applied because more than 3 males in gnomAD v2.1.1 are reported with this variant, as per CFD VCEP specifications (PMID: 23492913).
Curation History
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