13-113110713-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong
The NM_019616.4(F7):c.88C>T(p.His30Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000491 in 1,548,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000024 ( 0 hom. )
Consequence
F7
NM_019616.4 missense
NM_019616.4 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 0.645
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 Uncertain_significance. Variant got 0 ACMG points.
PM1
?
In a propeptide (size 39) in uniprot entity FA7_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_019616.4
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.05714211).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F7 | NM_019616.4 | c.88C>T | p.His30Tyr | missense_variant | 2/8 | ENST00000346342.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F7 | ENST00000346342.8 | c.88C>T | p.His30Tyr | missense_variant | 2/8 | 1 | NM_019616.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.000283 AC: 43AN: 152192Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000588 AC: 9AN: 152986Hom.: 0 AF XY: 0.0000123 AC XY: 1AN XY: 81046
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GnomAD4 exome AF: 0.0000236 AC: 33AN: 1396360Hom.: 0 Cov.: 31 AF XY: 0.0000131 AC XY: 9AN XY: 688744
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GnomAD4 genome ? AF: 0.000282 AC: 43AN: 152304Hom.: 0 Cov.: 33 AF XY: 0.000282 AC XY: 21AN XY: 74466
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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 submitter | clinical testing | Ambry Genetics | Jan 07, 2022 | The c.154C>T (p.H52Y) alteration is located in exon 3 (coding exon 3) of the F7 gene. This alteration results from a C to T substitution at nucleotide position 154, causing the histidine (H) at amino acid position 52 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
N;N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;D
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MVP
MPC
0.54
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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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