chr13-113105879-T-C

Position:

• chr13-113105879-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.991

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.

• PM2: Very rare variant in population databases, with high coverage
• 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/exons	MANE	UniProt
F7	NM_019616.4	c.38T>C	p.Leu13Pro	missense_variant	1/8	ENST00000346342.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F7	ENST00000346342.8	c.38T>C	p.Leu13Pro	missense_variant	1/8	1	NM_019616.4	P2
F7	ENST00000375581.3	c.38T>C	p.Leu13Pro	missense_variant	1/9	1		A2
F7	ENST00000541084.5	c.38T>C	p.Leu13Pro	missense_variant	1/6	2
F7	ENST00000444337.1	c.38T>C	p.Leu13Pro	missense_variant, NMD_transcript_variant	1/5	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000347 AC: 5 AN: 1439506 Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 2 AN XY: 713336

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000128

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Apr 01, 1998

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	24
DANN	Benign	0.73
DEOGEN2	Uncertain	0.54	.;.;D
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.34	T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.91	D;D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.2	.;M;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.55	T
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	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.63
gMVP		0.92

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: rs387906507; hg19: chr13-113760193;