13-113149146-C-T

Position:

chr13-113149146-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5

The NM_000504.4(F10):c.1096C>T(p.Arg366Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,656 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: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

F10
NM_000504.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.54

Variant links:

Genes affected

F10 (HGNC:3528): (coagulation factor X) This gene encodes the vitamin K-dependent coagulation factor X of the blood coagulation cascade. This factor undergoes multiple processing steps before its preproprotein is converted to a mature two-chain form by the excision of the tripeptide RKR. Two chains of the factor are held together by 1 or more disulfide bonds; the light chain contains 2 EGF-like domains, while the heavy chain contains the catalytic domain which is structurally homologous to those of the other hemostatic serine proteases. The mature factor is activated by the cleavage of the activation peptide by factor IXa (in the intrisic pathway), or by factor VIIa (in the extrinsic pathway). The activated factor then converts prothrombin to thrombin in the presence of factor Va, Ca+2, and phospholipid during blood clotting. Mutations of this gene result in factor X deficiency, a hemorrhagic condition of variable severity. 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]

F10 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM1

In a domain Peptidase S1 (size 232) in uniprot entity FA10_HUMAN there are 16 pathogenic changes around while only 0 benign (100%) in NM_000504.4

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.988

PP5

Variant 13-113149146-C-T is Pathogenic according to our data. Variant chr13-113149146-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 12053.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F10	NM_000504.4 linkuse as main transcript	c.1096C>T	p.Arg366Cys	missense_variant	8/8	ENST00000375559.8	NP_000495.1	P00742Q5JVE7
F10	NM_001312674.2 linkuse as main transcript	c.964C>T	p.Arg322Cys	missense_variant	7/7		NP_001299603.1	P00742
F10	NM_001312675.2 linkuse as main transcript	c.*87C>T		3_prime_UTR_variant	8/8		NP_001299604.1	P00742Q5JVE8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
F10	ENST00000375559.8 linkuse as main transcript	c.1096C>T	p.Arg366Cys	missense_variant	8/8	1	NM_000504.4	ENSP00000364709.3	P00742
F10	ENST00000375551.7 linkuse as main transcript	c.*87C>T		3_prime_UTR_variant	8/8	1		ENSP00000364701.3	Q5JVE8
F10	ENST00000409306.5 linkuse as main transcript	c.*87C>T		3_prime_UTR_variant	8/8	3		ENSP00000387092.1	B7ZBK1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249940

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135518

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000548

AC:

AN:

1460656

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726618

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Factor X deficiency

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 1989

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.89

Eigen

Benign

0.060

Eigen_PC

Benign

-0.096

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.97

M_CAP

Pathogenic

0.43

MetaRNN

Pathogenic

0.99

MetaSVM

Pathogenic

0.83

MutationAssessor

Uncertain

2.7

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-6.3

REVEL

Pathogenic

0.72

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.66

MutPred

0.87

Loss of MoRF binding (P = 6e-04);

MVP

0.94

MPC

1.7

ClinPred

0.99

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.80

gMVP

0.94

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over