chr13-113105879-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019616.4(F7):​c.38T>A​(p.Leu13His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,439,506 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

F7
NM_019616.4 missense

Scores

1
10
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.991
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]

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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;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
F7NM_019616.4 linkc.38T>A p.Leu13His missense_variant Exon 1 of 8 ENST00000346342.8 NP_062562.1 P08709-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
F7ENST00000346342.8 linkc.38T>A p.Leu13His missense_variant Exon 1 of 8 1 NM_019616.4 ENSP00000329546.4 P08709-2
F7ENST00000375581.3 linkc.38T>A p.Leu13His missense_variant Exon 1 of 9 1 ENSP00000364731.3 P08709-1
F7ENST00000541084.5 linkc.38T>A p.Leu13His missense_variant Exon 1 of 6 2 ENSP00000442051.2 F5H8B0
F7ENST00000444337.1 linkn.38T>A non_coding_transcript_exon_variant Exon 1 of 5 5 ENSP00000387669.1 E9PH36

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000462
AC:
1
AN:
216450
Hom.:
0
AF XY:
0.00000862
AC XY:
1
AN XY:
116000
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000383
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000139
AC:
2
AN:
1439506
Hom.:
0
Cov.:
31
AF XY:
0.00000280
AC XY:
2
AN XY:
713336
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000243
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.28
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Uncertain
24
DANN
Benign
0.80
DEOGEN2
Uncertain
0.54
.;.;D
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.61
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.32
T;T;T
M_CAP
Uncertain
0.15
D
MetaRNN
Uncertain
0.52
D;D;D
MetaSVM
Uncertain
-0.090
T
MutationAssessor
Uncertain
2.2
.;M;M
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-2.1
.;N;N
REVEL
Uncertain
0.38
Sift
Uncertain
0.019
.;D;D
Sift4G
Pathogenic
0.0
D;T;D
Polyphen
1.0, 1.0
.;D;D
Vest4
0.54
MutPred
0.45
Gain of catalytic residue at G14 (P = 0);Gain of catalytic residue at G14 (P = 0);Gain of catalytic residue at G14 (P = 0);
MVP
0.84
MPC
0.24
ClinPred
0.30
T
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.29
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs387906507; hg19: chr13-113760193; API