rs5962

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.399C>T(p.Asn133Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,614,112 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 63 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 72 hom. )

Consequence

F10
NM_000504.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.79

Publications

3 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=-0.66).

BP6

Variant 13-113140947-C-T is Benign according to our data. Variant chr13-113140947-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 311274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F10	NM_000504.4 link	c.399C>T	p.Asn133Asn	synonymous_variant	Exon 5 of 8	ENST00000375559.8	NP_000495.1	P00742Q5JVE7
F10	NM_001312675.2 link	c.399C>T	p.Asn133Asn	synonymous_variant	Exon 5 of 8		NP_001299604.1	P00742Q5JVE8
F10	NM_001312674.2 link	c.370+1477C>T		intron_variant	Intron 4 of 6		NP_001299603.1	P00742

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F10	ENST00000375559.8 link	c.399C>T	p.Asn133Asn	synonymous_variant	Exon 5 of 8	1	NM_000504.4	ENSP00000364709.3		P00742

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2586

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0565

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.0191

GnomAD2 exomes

AF:

0.00496

AC:

1247

AN:

251294

AF XY:

0.00387

show subpopulations

Gnomad AFR exome

AF:

0.0564

Gnomad AMR exome

AF:

0.00393

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00326

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000766

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00233

AC:

3403

AN:

1461764

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

1556

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.0557

AC:

1865

AN:

33480

American (AMR)

AF:

0.00458

AC:

205

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00145

AC:

AN:

26136

East Asian (EAS)

AF:

0.00176

AC:

AN:

39700

South Asian (SAS)

AF:

0.000162

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53296

Middle Eastern (MID)

AF:

0.00641

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000759

AC:

844

AN:

1112008

Other (OTH)

AF:

0.00546

AC:

330

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

206

411

617

822

1028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<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:

0.0170

AC:

2589

AN:

152348

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

1221

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0564

AC:

2347

AN:

41580

American (AMR)

AF:

0.00830

AC:

127

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00289

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000720

AC:

AN:

68036

Other (OTH)

AF:

0.0189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

129

259

388

518

647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00676

Hom.:

Bravo

AF:

0.0189

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000711

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary factor X deficiency disease

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.85

(source)

DANN

Benign

0.69

PhyloP100

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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