Evidence Repository - GenboreeKB

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001313913.2:c.1121G>C

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA414446711

Gene: F9

Condition: hemophilia B

Inheritance Mode: X-linked inheritance

Link to MONDO

UUID: 0b021702-fc7d-4df3-9f53-565427e3067c

Approved on: 2024-05-09

Published on: 2024-07-11

HGVS expressions

NM_001313913.2:c.1121G>C

NC_000023.11:g.139561920G>C

CM000685.2:g.139561920G>C

NC_000023.10:g.138644079G>C

CM000685.1:g.138644079G>C

NC_000023.9:g.138471745G>C

NG_007994.1:g.36185G>C

ENST00000218099.7:c.1235G>C

ENST00000643157.1:n.1723+179G>C

ENST00000218099.6:c.1235G>C

ENST00000394090.2:c.1121G>C

NM_000133.3:c.1235G>C

NM_001313913.1:c.1121G>C

NM_000133.4:c.1235G>C

Uncertain Significance

PS4_Supporting PP3 PM5 PM2_Supporting

Evidence Links 0

Expert Panel

Coagulation Factor Deficiency VCEP

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.1235G>C (NM_000133.4) variant in F9 is a missense variant predicted to cause substitution of Glycine by Alanine at amino acid 412 (p.Gly412Ala). This variant has been reported in at least 1 proband meeting the hemophilia B phenotype criteria specified by the Coagulation Factor Deficiency VCEP (PS4_Supporting; PMID: 11013449). This variant is absent from gnomAD v2.1.1 and v3.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.984, which is above the threshold of 0.6, evidence that correlates with impact to F9 function (PP3). In summary, this variant meets the criteria to be classified as Uncertain Significance for X-linked recessive hemophilia B based on the ACMG/AMP criteria applied, as specified by the ClinGen Coagulation Factor Deficiency VCEP: PM5, PP3, PS4_Supporting, PM2_Supporting. (ClinGen Coagulation Factor Deficiency Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for F9 Version 1.0.0., Released 10/5/2023)

PS4_Supporting

This variant has been reported in at least 1 proband meeting the hemophilia B phenotype criteria specified by the Coagulation Factor Deficiency VCEP (PS4_Supporting; PMID: 11013449).

PP3

The computational predictor REVEL gives a score of 0.984, which is above the threshold of 0.6, evidence that correlates with impact to F9 function (PP3). SpliceAI predicts no splicing impact with delta score of 0.

PM5

Another missense variant c.1235G>A, p.Gly412Glu in the same codon has been classified as pathogenic for hemophilia B by the ClinGen Coagulation Factor Deficiency VCEP (PM5).

PM2_Supporting

This variant is absent from gnomAD v2.1.1 and v3.1.1 (PM2_Supporting).

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.