rs118203906
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 5P and 2B. PM5PP3_ModeratePP5BS1_SupportingBS2_Supporting
The NM_000130.5(F5):āc.1001G>Cā(p.Arg334Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,614,068 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R334G) has been classified as Likely benign.
Frequency
Consequence
NM_000130.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F5 | NM_000130.5 | c.1001G>C | p.Arg334Thr | missense_variant | 7/25 | ENST00000367797.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F5 | ENST00000367797.9 | c.1001G>C | p.Arg334Thr | missense_variant | 7/25 | 1 | NM_000130.5 | P2 | |
F5 | ENST00000367796.3 | c.1001G>C | p.Arg334Thr | missense_variant | 7/25 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152098Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000227 AC: 57AN: 251352Hom.: 1 AF XY: 0.000213 AC XY: 29AN XY: 135844
GnomAD4 exome AF: 0.000130 AC: 190AN: 1461852Hom.: 2 Cov.: 31 AF XY: 0.000133 AC XY: 97AN XY: 727226
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152216Hom.: 0 Cov.: 31 AF XY: 0.0000537 AC XY: 4AN XY: 74428
ClinVar
Submissions by phenotype
Thrombophilia due to activated protein C resistance Pathogenic:2Other:1
Pathogenic, no assertion criteria provided | clinical testing | Breakthrough Genomics, Breakthrough Genomics | - | This variant was previously reported in a proximal deep vein thrombosis patient of British origin and was also identified in his mother, who presented with abnormally low APC resistance value. It was not found in 600 other individuals presenting with thromboembolism or in a population of normal blood donors, suggesting that it is a rare factor V variant [PMID: 9454742]. This variant was previously represented as either p.R306T/Arg306Thr or F5 Cambridge in the cited articles. Another missense substitution affecting this residue p. Arg334Gly (referred as Arg306Gly FV Hong Kong) was previously identified in 2 thrombotic patients and 1 nonthrombotic subject of Chinese origin [PMID: 9454741]. Previously this variant was reported to affect the cleavage site responsible for the complete loss of F5 procoagulant activity suggesting its possible contribution to APC resistance [PMID: 30630204, 7989361]. However, invitro recombinant cells harboring this variant revealed intermediate APC resistance patterns between those of wild type factor V and other well-known F5 Leiden (Arg506) variant, suggesting low thrombotic risk association [PMID:12091344]. - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 15, 1998 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at