13-113105879-T-C

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP2PP3_ModeratePP5

The NM_019616.4(F7):c.38T>C(p.Leu13Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000347 in 1,439,506 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 (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

F7
NM_019616.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.991

Publications

4 publications found

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]

F7 Gene-Disease associations (from GenCC):

congenital factor VII deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Orphanet, Ambry Genetics
factor VII deficiency
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

F7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 39 curated pathogenic missense variants (we use a threshold of 10). The gene has 9 curated benign missense variants. Gene score misZ: 0.31991 (below the threshold of 3.09). Trascript score misZ: 0.36088 (below the threshold of 3.09). GenCC associations: The gene is linked to congenital factor VII deficiency, factor VII deficiency.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.911

PP5

Variant 13-113105879-T-C is Pathogenic according to our data. Variant chr13-113105879-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 12075.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F7	NM_019616.4 link	c.38T>C	p.Leu13Pro	missense_variant	Exon 1 of 8	ENST00000346342.8	NP_062562.1	P08709-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
F7	ENST00000346342.8 link	c.38T>C	p.Leu13Pro	missense_variant	Exon 1 of 8	1	NM_019616.4	ENSP00000329546.4	P08709-2
F7	ENST00000375581.3 link	c.38T>C	p.Leu13Pro	missense_variant	Exon 1 of 9	1		ENSP00000364731.3	P08709-1
F7	ENST00000541084.5 link	c.38T>C	p.Leu13Pro	missense_variant	Exon 1 of 6	2		ENSP00000442051.2	F5H8B0
F7	ENST00000444337.1 link	n.38T>C		non_coding_transcript_exon_variant	Exon 1 of 5	5		ENSP00000387669.1	E9PH36

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

216450

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000347

AC:

AN:

1439506

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

713336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33380

American (AMR)

AF:

0.00

AC:

AN:

41510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25492

East Asian (EAS)

AF:

0.000128

AC:

AN:

39124

South Asian (SAS)

AF:

0.00

AC:

AN:

82192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50650

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101768

Other (OTH)

AF:

0.00

AC:

AN:

59656

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Factor VII deficiency

Pathogenic:1

Apr 01, 1998

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.26

CADD

Uncertain

(source)

DANN

Benign

0.73

DEOGEN2

Uncertain

0.54

.;.;D

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.34

T;T;T

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.91

D;D;D

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.2

.;M;M

PhyloP100

0.99

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.9

.;N;N

REVEL

Uncertain

0.54

Sift

Uncertain

0.022

.;D;D

Sift4G

Pathogenic

0.0

D;T;D

Polyphen

0.053, 0.031

.;B;B

Vest4

0.68

MutPred

0.83

Gain of catalytic residue at Q16 (P = 0);Gain of catalytic residue at Q16 (P = 0);Gain of catalytic residue at Q16 (P = 0);

MVP

0.64

MPC

0.30

ClinPred

0.15

GERP RS

1.6

PromoterAI

0.023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.63

gMVP

0.92

Mutation Taster

=15/85

disease causing (ClinVar)

(source)

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

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13-113105879-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over