rs3211719

Variant names:

• chr13-113123195-A-G
• rs3211719
• NM_000504.4:c.70+270A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000504.4(F10):​c.70+270A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,112 control chromosomes in the GnomAD database, including 3,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3657 hom., cov: 32)
• Consequence: F10 NM_000504.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.427
• Publications: 13 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-113123195-A-G is Benign according to our data. Variant chr13-113123195-A-G is described in ClinVar as Benign. ClinVar VariationId is 1249655.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000504.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F10	NM_000504.4	MANE Select	c.70+270A>G		intron	N/A	NP_000495.1
	F10	NM_001312674.2		c.70+270A>G		intron	N/A	NP_001299603.1
	F10	NM_001312675.2		c.70+270A>G		intron	N/A	NP_001299604.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F10	ENST00000375559.8	TSL:1 MANE Select	c.70+270A>G		intron	N/A	ENSP00000364709.3
	F10	ENST00000375551.7	TSL:1	c.70+270A>G		intron	N/A	ENSP00000364701.3
	F10	ENST00000410083.6	TSL:1	n.70+270A>G		intron	N/A	ENSP00000386320.2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32313 AN: 151994 Hom.: 3651 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.198

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.213 AC: 32348 AN: 152112 Hom.: 3657 Cov.: 32 AF XY: 0.210 AC XY: 15589 AN XY: 74376

African (AFR) AF: 0.170 AC: 7060 AN: 41490

American (AMR) AF: 0.165 AC: 2526 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 829 AN: 3472

East Asian (EAS) AF: 0.304 AC: 1570 AN: 5162

South Asian (SAS) AF: 0.168 AC: 810 AN: 4826

European-Finnish (FIN) AF: 0.188 AC: 1989 AN: 10592

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16809 AN: 67972

Other (OTH) AF: 0.198 AC: 418 AN: 2108

Alfa AF: 0.233 Hom.: 6873

Bravo AF: 0.209

Asia WGS AF: 0.230 AC: 798 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.65
PhyloP100		-0.43
PromoterAI		0.11	Neutral
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: rs3211719; hg19: chr13-113777509;