13-113130129-G-C

Position:

• chr13-113130129-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000504.4(F10):​c.231+517G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 193,390 control chromosomes in the GnomAD database, including 32,778 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (24814 hom., cov: 35)
  • Exomes 𝑓: 0.59 (7964 hom.)
• Consequence: F10 NM_000504.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F10	NM_000504.4	c.231+517G>C		intron_variant		ENST00000375559.8	NP_000495.1
F10	NM_001312674.2	c.231+517G>C		intron_variant			NP_001299603.1
F10	NM_001312675.2	c.231+517G>C		intron_variant			NP_001299604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F10	ENST00000375559.8	c.231+517G>C		intron_variant		1	NM_000504.4	ENSP00000364709.3

Frequencies

GnomAD3 genomes AF: 0.575 AC: 85949 AN: 149460 Hom.: 24794 Cov.: 35

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.676

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.588

GnomAD4 exome AF: 0.594 AC: 26039 AN: 43820 Hom.: 7964 Cov.: 0 AF XY: 0.604 AC XY: 13592 AN XY: 22494

Gnomad4 AFR exome AF: 0.479

Gnomad4 AMR exome AF: 0.533

Gnomad4 ASJ exome AF: 0.753

Gnomad4 EAS exome AF: 0.499

Gnomad4 SAS exome AF: 0.689

Gnomad4 FIN exome AF: 0.485

Gnomad4 NFE exome AF: 0.597

Gnomad4 OTH exome AF: 0.590

GnomAD4 genome AF: 0.575 AC: 86007 AN: 149570 Hom.: 24814 Cov.: 35 AF XY: 0.571 AC XY: 41758 AN XY: 73182

Gnomad4 AFR AF: 0.495

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.589

Alfa AF: 0.454 Hom.: 1257

Bravo AF: 0.570

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.73
DANN	Benign	0.45

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

Other links and lift over

dbSNP: rs693335; hg19: chr13-113784443;