13-113147423-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000504.4(F10):c.792C>T(p.Thr264Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 1,612,706 control chromosomes in the GnomAD database, including 552,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 42074 hom., cov: 31)

Exomes 𝑓: 0.83 ( 510602 hom. )

Consequence

F10
NM_000504.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.404

Publications

32 publications found

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 Gene-Disease associations (from GenCC):

congenital factor X deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

F10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 13-113147423-C-T is Benign according to our data. Variant chr13-113147423-C-T is described in ClinVar as Benign. ClinVar VariationId is 256308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.404 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F10	NM_000504.4 link	c.792C>T	p.Thr264Thr	synonymous_variant	Exon 7 of 8	ENST00000375559.8	NP_000495.1	P00742Q5JVE7
F10	NM_001312674.2 link	c.660C>T	p.Thr220Thr	synonymous_variant	Exon 6 of 7		NP_001299603.1	P00742
F10	NM_001312675.2 link	c.792C>T	p.Thr264Thr	synonymous_variant	Exon 7 of 8		NP_001299604.1	P00742Q5JVE8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F10	ENST00000375559.8 link	c.792C>T	p.Thr264Thr	synonymous_variant	Exon 7 of 8	1	NM_000504.4	ENSP00000364709.3		P00742

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110222

AN:

151928

Hom.:

42077

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.942

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.882

Gnomad EAS

AF:

0.510

Gnomad SAS

AF:

0.704

Gnomad FIN

AF:

0.819

Gnomad MID

AF:

0.825

Gnomad NFE

AF:

0.862

Gnomad OTH

AF:

0.744

GnomAD2 exomes

AF:

0.758

AC:

190425

AN:

251204

AF XY:

0.769

show subpopulations

Gnomad AFR exome

AF:

0.488

Gnomad AMR exome

AF:

0.634

Gnomad ASJ exome

AF:

0.888

Gnomad EAS exome

AF:

0.492

Gnomad FIN exome

AF:

0.825

Gnomad NFE exome

AF:

0.864

Gnomad OTH exome

AF:

0.795

GnomAD4 exome

AF:

0.831

AC:

1213187

AN:

1460660

Hom.:

510602

Cov.:

AF XY:

0.829

AC XY:

602435

AN XY:

726676

show subpopulations

African (AFR)

AF:

0.485

AC:

16209

AN:

33442

American (AMR)

AF:

0.643

AC:

28727

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.884

AC:

23080

AN:

26116

East Asian (EAS)

AF:

0.546

AC:

21677

AN:

39682

South Asian (SAS)

AF:

0.713

AC:

61450

AN:

86216

European-Finnish (FIN)

AF:

0.826

AC:

44083

AN:

53398

Middle Eastern (MID)

AF:

0.855

AC:

4928

AN:

5762

European-Non Finnish (NFE)

AF:

0.868

AC:

964690

AN:

1110986

Other (OTH)

AF:

0.801

AC:

48343

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

10013

20025

30038

40050

50063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21058

42116

63174

84232

105290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.725

AC:

110246

AN:

152046

Hom.:

42074

Cov.:

AF XY:

0.720

AC XY:

53520

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.495

AC:

20484

AN:

41416

American (AMR)

AF:

0.702

AC:

10734

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.882

AC:

3064

AN:

3472

East Asian (EAS)

AF:

0.510

AC:

2627

AN:

5152

South Asian (SAS)

AF:

0.704

AC:

3388

AN:

4814

European-Finnish (FIN)

AF:

0.819

AC:

8674

AN:

10596

Middle Eastern (MID)

AF:

0.825

AC:

241

AN:

292

European-Non Finnish (NFE)

AF:

0.862

AC:

58611

AN:

67998

Other (OTH)

AF:

0.741

AC:

1566

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1370

2739

4109

5478

6848

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.815

Hom.:

204964

Bravo

AF:

0.708

Asia WGS

AF:

0.572

AC:

1994

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Hereditary factor X deficiency disease

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.3

(source)

DANN

Benign

0.33

PhyloP100

-0.40

Mutation Taster

=100/0

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over