Menu
GeneBe

rs6025

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PM5BP4_Moderate

The NM_000130.5(F5):c.1601G>T(p.Arg534Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R534Q) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Consequence

F5
NM_000130.5 missense

Scores

2
1
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.48
Variant links:
Genes affected
F5 (HGNC:3542): (coagulation factor V) This gene encodes an essential cofactor of the blood coagulation cascade. This factor circulates in plasma, and is converted to the active form by the release of the activation peptide by thrombin during coagulation. This generates a heavy chain and a light chain which are held together by calcium ions. The activated protein is a cofactor that participates with activated coagulation factor X to activate prothrombin to thrombin. Defects in this gene result in either an autosomal recessive hemorrhagic diathesis or an autosomal dominant form of thrombophilia, which is known as activated protein C resistance. [provided by RefSeq, Oct 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr1-169549811-C-T is described in ClinVar as [drug_response]. Clinvar id is 642.Status of the report is reviewed_by_expert_panel, 3 stars. We mark this variant Likely_pathogenic, oryginal submissions are: {Pathogenic=12, risk_factor=1, Benign=1, Pathogenic_low_penetrance=1, drug_response=1}.
BP4
Computational evidence support a benign effect (MetaRNN=0.23257288).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
F5NM_000130.5 linkuse as main transcriptc.1601G>T p.Arg534Leu missense_variant 10/25 ENST00000367797.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
F5ENST00000367797.9 linkuse as main transcriptc.1601G>T p.Arg534Leu missense_variant 10/251 NM_000130.5 P2
F5ENST00000367796.3 linkuse as main transcriptc.1601G>T p.Arg534Leu missense_variant 10/255 A2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.64
BayesDel_noAF
Pathogenic
0.15
Cadd
Uncertain
25
DEOGEN2
Benign
0.42
T;T
LIST_S2
Benign
0.83
T;T
MetaRNN
Benign
0.23
T;T
Sift4G
Uncertain
0.0060
D;D
Vest4
0.34
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.89

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.23
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.23
Position offset: 25

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6025; hg19: chr1-169519049; API