NM_005141.5:c.586C>T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PS1_ModeratePM2PP3_Strong
The NM_005141.5(FGB):c.586C>T(p.Arg196Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,254 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 Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in UniProt.
Frequency
Consequence
NM_005141.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251178Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135746
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461254Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726994
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
FGB-related disorder Pathogenic:1
The FGB c.586C>T variant is predicted to result in the amino acid substitution p.Arg196Cys. This variant has been reported in multiple individuals with congenital dysfibrinogenemia (Lounes et al. 2001. PubMed ID: 11468164; Chinni et al. 2018. PubMed ID: 30418131; Table S3, Downes et al. 2019. PubMed ID: 31064749; Table S3, Gindele et al. 2021. PubMed ID: 33807613; Simurda et al. 2024. PubMed ID: 38251440). In vitro studies suggest that this variant disrupts fibrinogen polymerization, leading to impaired clot formation (Lounes et al. 2001. PubMed ID: 11468164). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Taken together, this variant is interpreted as likely pathogenic. -
Hypofibrinogenemia Uncertain:1
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FIBRINOGEN LONGMONT Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at