13-113106877-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000131.4(F7):​c.97C>T​(p.Arg33Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,606,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

F7
NM_000131.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.101
Variant links:
Genes affected
F7 (HGNC:3544): (coagulation factor VII) This gene encodes coagulation factor VII which is a vitamin K-dependent factor essential for hemostasis. This factor circulates in the blood in a zymogen form, and is converted to an active form by either factor IXa, factor Xa, factor XIIa, or thrombin by minor proteolysis. Upon activation of the factor VII, a heavy chain containing a catalytic domain and a light chain containing 2 EGF-like domains are generated, and two chains are held together by a disulfide bond. In the presence of factor III and calcium ions, the activated factor then further activates the coagulation cascade by converting factor IX to factor IXa and/or factor X to factor Xa. Defects in this gene can cause coagulopathy. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing to generate mature polypeptides. [provided by RefSeq, Aug 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07121283).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
F7NM_019616.4 linkc.64+972C>T intron_variant ENST00000346342.8 NP_062562.1 P08709-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
F7ENST00000375581.3 linkc.97C>T p.Arg33Trp missense_variant 2/91 ENSP00000364731.3 P08709-1
F7ENST00000346342.8 linkc.64+972C>T intron_variant 1 NM_019616.4 ENSP00000329546.4 P08709-2
F7ENST00000541084.5 linkc.64+972C>T intron_variant 2 ENSP00000442051.2 F5H8B0
F7ENST00000444337.1 linkn.64+972C>T intron_variant 5 ENSP00000387669.1 E9PH36

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152000
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000842
AC:
2
AN:
237420
Hom.:
0
AF XY:
0.00000775
AC XY:
1
AN XY:
129102
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000297
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000939
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000124
AC:
18
AN:
1454634
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
723014
show subpopulations
Gnomad4 AFR exome
AF:
0.000150
Gnomad4 AMR exome
AF:
0.0000227
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000631
Gnomad4 OTH exome
AF:
0.0000666
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152000
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74230
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000333
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 12, 2024The c.97C>T (p.R33W) alteration is located in exon 2 (coding exon 2) of the F7 gene. This alteration results from a C to T substitution at nucleotide position 97, causing the arginine (R) at amino acid position 33 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
0.34
DANN
Benign
0.81
DEOGEN2
Benign
0.28
T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0017
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.071
T
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.060
N
REVEL
Benign
0.15
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.016
D
Polyphen
0.0
B
Vest4
0.063
MutPred
0.40
Gain of catalytic residue at P36 (P = 0);
MVP
0.72
MPC
0.20
ClinPred
0.046
T
GERP RS
-1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.045
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
Details are displayed if max score is > 0.2

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: rs764010176; hg19: chr13-113761191; API