chr13-113147423-C-T

Position:

chr13-113147423-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000375559.8(F10):c.792C>T(p.Thr264=) 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
ENST00000375559.8 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.404

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 Benign. Variant got -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 id is 256308.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-113147423-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein
F10	NM_000504.4 linkuse as main transcript	c.792C>T	p.Thr264=	synonymous_variant	7/8	ENST00000375559.8	NP_000495.1
F10	NM_001312674.2 linkuse as main transcript	c.660C>T	p.Thr220=	synonymous_variant	6/7		NP_001299603.1
F10	NM_001312675.2 linkuse as main transcript	c.792C>T	p.Thr264=	synonymous_variant	7/8		NP_001299604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F10	ENST00000375559.8 linkuse as main transcript	c.792C>T	p.Thr264=	synonymous_variant	7/8	1	NM_000504.4	ENSP00000364709	P1

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

GnomAD3 exomes

AF:

0.758

AC:

190425

AN:

251204

Hom.:

74687

AF XY:

0.769

AC XY:

104494

AN XY:

135826

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 SAS exome

AF:

0.708

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

Gnomad4 AFR exome

AF:

0.485

Gnomad4 AMR exome

AF:

0.643

Gnomad4 ASJ exome

AF:

0.884

Gnomad4 EAS exome

AF:

0.546

Gnomad4 SAS exome

AF:

0.713

Gnomad4 FIN exome

AF:

0.826

Gnomad4 NFE exome

AF:

0.868

Gnomad4 OTH exome

AF:

0.801

GnomAD4 genome

AF:

0.725

AC:

110246

AN:

152046

Hom.:

42074

Cov.:

AF XY:

0.720

AC XY:

53520

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.495

Gnomad4 AMR

AF:

0.702

Gnomad4 ASJ

AF:

0.882

Gnomad4 EAS

AF:

0.510

Gnomad4 SAS

AF:

0.704

Gnomad4 FIN

AF:

0.819

Gnomad4 NFE

AF:

0.862

Gnomad4 OTH

AF:

0.741

Alfa

AF:

0.835

Hom.:

92193

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Hereditary factor X deficiency disease

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.3

DANN

Benign

0.33

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