rs3211770

Positions:

• chr13-113139535-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F10	NM_000504.4	c.370+65G>A		intron_variant		ENST00000375559.8	NP_000495.1
F10	NM_001312674.2	c.370+65G>A		intron_variant			NP_001299603.1
F10	NM_001312675.2	c.370+65G>A		intron_variant			NP_001299604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F10	ENST00000375559.8	c.370+65G>A		intron_variant		1	NM_000504.4	ENSP00000364709.3

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

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.0785

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.0190

Gnomad4 SAS exome AF: 0.193

Gnomad4 FIN exome AF: 0.0856

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.119

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

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.0147

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.0806

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.126

Alfa AF: 0.122 Hom.: 765

Bravo AF: 0.115

Asia WGS AF: 0.0880 AC: 308 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs3211770; hg19: chr13-113793849; COSMIC: COSV65022651; COSMIC: COSV65022651;