chr13-113138440-T-C

Variant names:

• chr13-113138440-T-C
• rs2251102
• NM_000504.4:c.232-17T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000504.4(F10):​c.232-17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 1,178,712 control chromosomes in the GnomAD database, including 410,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (48841 hom., cov: 33)
  • Exomes 𝑓: 0.84 (361524 hom.)
• Consequence: F10 NM_000504.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.31
• Publications: 8 publications found

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

ENSG00000297191 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-113138440-T-C is Benign according to our data. Variant chr13-113138440-T-C is described in CliVar as Benign. Clinvar id is 256307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-113138440-T-C is described in CliVar as Benign. Clinvar id is 256307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-113138440-T-C is described in CliVar as Benign. Clinvar id is 256307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-113138440-T-C is described in CliVar as Benign. Clinvar id is 256307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-113138440-T-C is described in CliVar as Benign. Clinvar id is 256307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-113138440-T-C is described in CliVar as Benign. Clinvar id is 256307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-113138440-T-C is described in CliVar as Benign. Clinvar id is 256307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-113138440-T-C is described in CliVar as Benign. Clinvar id is 256307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-113138440-T-C is described in CliVar as Benign. Clinvar id is 256307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F10	NM_000504.4	c.232-17T>C		intron_variant	Intron 2 of 7	ENST00000375559.8	NP_000495.1
F10	NM_001312674.2	c.232-17T>C		intron_variant	Intron 2 of 6		NP_001299603.1
F10	NM_001312675.2	c.232-17T>C		intron_variant	Intron 2 of 7		NP_001299604.1
LOC124903215	XR_007063879.1	n.298-559A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F10	ENST00000375559.8	c.232-17T>C		intron_variant	Intron 2 of 7	1	NM_000504.4	ENSP00000364709.3

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121197 AN: 152024 Hom.: 48802 Cov.: 33

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.799

GnomAD2 exomes AF: 0.842 AC: 202335 AN: 240164 AF XY: 0.844

Gnomad AFR exome AF: 0.655

Gnomad AMR exome AF: 0.913

Gnomad ASJ exome AF: 0.835

Gnomad EAS exome AF: 0.888

Gnomad FIN exome AF: 0.847

Gnomad NFE exome AF: 0.841

Gnomad OTH exome AF: 0.840

GnomAD4 exome AF: 0.838 AC: 860113 AN: 1026570 Hom.: 361524 Cov.: 14 AF XY: 0.839 AC XY: 443520 AN XY: 528396

African (AFR) AF: 0.642 AC: 16036 AN: 24964

American (AMR) AF: 0.908 AC: 37093 AN: 40844

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 18986 AN: 22690

East Asian (EAS) AF: 0.912 AC: 33970 AN: 37258

South Asian (SAS) AF: 0.847 AC: 61623 AN: 72728

European-Finnish (FIN) AF: 0.842 AC: 43778 AN: 51980

Middle Eastern (MID) AF: 0.798 AC: 3328 AN: 4172

European-Non Finnish (NFE) AF: 0.836 AC: 607773 AN: 726664

Other (OTH) AF: 0.829 AC: 37526 AN: 45270

GnomAD4 genome AF: 0.797 AC: 121287 AN: 152142 Hom.: 48841 Cov.: 33 AF XY: 0.799 AC XY: 59426 AN XY: 74388

African (AFR) AF: 0.664 AC: 27538 AN: 41458

American (AMR) AF: 0.864 AC: 13224 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2928 AN: 3468

East Asian (EAS) AF: 0.895 AC: 4632 AN: 5178

South Asian (SAS) AF: 0.835 AC: 4034 AN: 4830

European-Finnish (FIN) AF: 0.847 AC: 8958 AN: 10576

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.843 AC: 57344 AN: 68010

Other (OTH) AF: 0.799 AC: 1688 AN: 2112

Alfa AF: 0.819 Hom.: 13786

Bravo AF: 0.794

Asia WGS AF: 0.822 AC: 2853 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

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

- -

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

- -

Hereditary factor X deficiency disease Benign:1

Aug 10, 2021

Genome-Nilou Lab

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	-0.86
CADD	Benign	0.70
DANN	Benign	0.68
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2251102; hg19: chr13-113792754;