13-113118845-G-C

Position:

• chr13-113118845-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_019616.4(F7):​c.1172G>C​(p.Arg391Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R391Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: F7 NM_019616.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a strand (size 4) in uniprot entity FA7_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_019616.4
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F7	NM_019616.4	c.1172G>C	p.Arg391Pro	missense_variant	8/8	ENST00000346342.8	NP_062562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F7	ENST00000346342.8	c.1172G>C	p.Arg391Pro	missense_variant	8/8	1	NM_019616.4	ENSP00000329546.4
F7	ENST00000375581.3	c.1238G>C	p.Arg413Pro	missense_variant	9/9	1		ENSP00000364731.3
F7	ENST00000541084.5	c.986G>C	p.Arg329Pro	missense_variant	6/6	2		ENSP00000442051.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Uncertain	0.72	.;.;D
Eigen	Benign	-0.81
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.64	T;T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.42	.;.;N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.3	.;D;D
REVEL	Uncertain	0.50
Sift	Benign	0.030	.;D;D
Sift4G	Uncertain	0.034	D;D;D
Polyphen		0.99, 0.99	.;D;D
Vest4		0.67
MutPred		0.60		.;.;Gain of catalytic residue at Y412 (P = 0);
MVP		0.79
MPC		0.80
ClinPred		0.70	D
GERP RS		-4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.88
gMVP		0.89

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: rs6046; hg19: chr13-113773159;