rs121913087
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PM1PM2PM5PP3_StrongPP5_Very_Strong
The NM_021870.3(FGG):c.901C>T(p.Arg301Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R301H) has been classified as Pathogenic.
Frequency
Consequence
NM_021870.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FGG | NM_021870.3 | c.901C>T | p.Arg301Cys | missense_variant | 8/9 | ENST00000336098.8 | |
FGG | NM_000509.6 | c.901C>T | p.Arg301Cys | missense_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FGG | ENST00000336098.8 | c.901C>T | p.Arg301Cys | missense_variant | 8/9 | 2 | NM_021870.3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461054Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726784
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Familial dysfibrinogenemia Pathogenic:3
Likely pathogenic, criteria provided, single submitter | clinical testing | Genetics and Molecular Pathology, SA Pathology | Apr 13, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 03, 2023 | Variant summary: FGG c.901C>T (p.Arg301Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250032 control chromosomes. c.901C>T has been reported in the literature in multiple individuals affected with congenital dysfibrinogenemia and/or comprehensively sequenced cohorts of patients with bleeding, thrombotic, and platelet disorders (example, PMID: 7654933, 31064749, 10911375, 29351094). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been ascertained in the context of this evaluation. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology | - | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 26, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Aug 18, 2022 | PP3, PM1, PM2, PM5, PS3, PS4_moderate - |
Hypofibrinogenemia Pathogenic:1
Pathogenic, criteria provided, single submitter | research | NIHR Bioresource Rare Diseases, University of Cambridge | Feb 01, 2019 | - - |
Afibrinogenemia Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology | - | - - |
FIBRINOGEN TOKYO 2 Other:1
other, no assertion criteria provided | literature only | OMIM | Sep 26, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at