rs3211770

Variant names:

• chr13-113139535-G-A
• rs3211770
• NM_000504.4:c.370+65G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-113139535-G-A
• chr13-113139535-G-T

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.370+65G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,287,960 control chromosomes in the GnomAD database, including 9,621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1060 hom., cov: 32)
  • Exomes 𝑓: 0.12 (8561 hom.)
• Consequence: F10 NM_000504.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.49
• Publications: 18 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, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

LOC124903215 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 13-113139535-G-A is Benign according to our data. Variant chr13-113139535-G-A is described in ClinVar as Benign. ClinVar VariationId is 1289702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.171 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F10	NM_000504.4	MANE Select	c.370+65G>A		intron	N/A	NP_000495.1	Q5JVE7
	F10	NM_001312674.2		c.370+65G>A		intron	N/A	NP_001299603.1
	F10	NM_001312675.2		c.370+65G>A		intron	N/A	NP_001299604.1	Q5JVE8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F10	ENST00000375559.8	TSL:1 MANE Select	c.370+65G>A		intron	N/A	ENSP00000364709.3	P00742
	F10	ENST00000375551.7	TSL:1	c.370+65G>A		intron	N/A	ENSP00000364701.3	Q5JVE8
	F10	ENST00000410083.6	TSL:1	n.370+65G>A		intron	N/A	ENSP00000386320.2	F8WBM7

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17194 AN: 151906 Hom.: 1060 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0147

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.0806

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.117 AC: 133187 AN: 1135936 Hom.: 8561 AF XY: 0.121 AC XY: 70003 AN XY: 578324

African (AFR) AF: 0.113 AC: 3077 AN: 27144

American (AMR) AF: 0.0785 AC: 3288 AN: 41908

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 4435 AN: 23886

East Asian (EAS) AF: 0.0190 AC: 709 AN: 37398

South Asian (SAS) AF: 0.193 AC: 15212 AN: 78740

European-Finnish (FIN) AF: 0.0856 AC: 4389 AN: 51254

Middle Eastern (MID) AF: 0.176 AC: 900 AN: 5120

European-Non Finnish (NFE) AF: 0.116 AC: 95254 AN: 820914

Other (OTH) AF: 0.119 AC: 5923 AN: 49572

GnomAD4 genome AF: 0.113 AC: 17203 AN: 152024 Hom.: 1060 Cov.: 32 AF XY: 0.112 AC XY: 8358 AN XY: 74326

African (AFR) AF: 0.114 AC: 4717 AN: 41450

American (AMR) AF: 0.107 AC: 1627 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 686 AN: 3468

East Asian (EAS) AF: 0.0147 AC: 76 AN: 5172

South Asian (SAS) AF: 0.181 AC: 870 AN: 4800

European-Finnish (FIN) AF: 0.0806 AC: 852 AN: 10574

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

European-Non Finnish (NFE) AF: 0.117 AC: 7975 AN: 67970

Other (OTH) AF: 0.126 AC: 266 AN: 2116

Alfa AF: 0.118 Hom.: 2733

Bravo AF: 0.115

Asia WGS AF: 0.0880 AC: 308 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.59
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3211770; hg19: chr13-113793849; COSMIC: COSV65022651; COSMIC: COSV65022651;