13-113118772-T-G
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_019616.4(F7):āc.1099T>Gā(p.Cys367Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,460,948 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 Pathogenic (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.0000034 ( 0 hom. )
Consequence
F7
NM_019616.4 missense
NM_019616.4 missense
Scores
14
2
3
Clinical Significance
Conservation
PhyloP100: 6.04
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PM1
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 2 uncertain in NM_019616.4
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.99
PP5
Variant 13-113118772-T-G is Pathogenic according to our data. Variant chr13-113118772-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 12085.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F7 | NM_019616.4 | c.1099T>G | p.Cys367Gly | missense_variant | 8/8 | ENST00000346342.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F7 | ENST00000346342.8 | c.1099T>G | p.Cys367Gly | missense_variant | 8/8 | 1 | NM_019616.4 | P2 | |
F7 | ENST00000375581.3 | c.1165T>G | p.Cys389Gly | missense_variant | 9/9 | 1 | A2 | ||
F7 | ENST00000541084.5 | c.913T>G | p.Cys305Gly | missense_variant | 6/6 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249480Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135414
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460948Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 726772
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GnomAD4 genome Cov.: 33
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33
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Factor VII deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2000 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Benign
DEOGEN2
Pathogenic
.;.;D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
.;.;H
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;D;D
REVEL
Pathogenic
Sift
Pathogenic
.;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
1.0
.;D;D
Vest4
MutPred
0.89
.;.;Gain of catalytic residue at S393 (P = 0);
MVP
MPC
0.83
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at