rs387906508

chr13-113118590-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP5

The NM_019616.4(F7):c.917T>C(p.Phe306Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: F7 NM_019616.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.01

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a domain Peptidase S1 (size 239) in uniprot entity FA7_HUMAN there are 97 pathogenic changes around while only 10 benign (91%) in NM_019616.4
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 13-113118590-T-C is Pathogenic according to our data. Variant chr13-113118590-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 12090.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F7	NM_019616.4	c.917T>C	p.Phe306Ser	missense_variant	8/8	ENST00000346342.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F7	ENST00000346342.8	c.917T>C	p.Phe306Ser	missense_variant	8/8	1	NM_019616.4	P2
F7	ENST00000375581.3	c.983T>C	p.Phe328Ser	missense_variant	9/9	1		A2
F7	ENST00000541084.5	c.731T>C	p.Phe244Ser	missense_variant	6/6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Factor VII deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 29, 1996

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Benign	0.081
Eigen_PC	Benign	0.013
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Uncertain	-0.021	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.52	T
REVEL	Uncertain	0.54
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.44
MutPred		0.55		.;.;Gain of catalytic residue at L323 (P = 0);
MVP		0.93
MPC		1.0
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.94
gMVP		0.90

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

Other links and lift over

dbSNP: rs387906508; hg19: chr13-113772904;