NM_000504.4:c.231+517G>C

Variant names:

• chr13-113130129-G-C
• rs693335
• NM_000504.4:c.231+517G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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-AS1 (HGNC:40225): (F10 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

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.231+517G>C		intron	N/A	NP_000495.1
	F10	NM_001312674.2		c.231+517G>C		intron	N/A	NP_001299603.1
	F10	NM_001312675.2		c.231+517G>C		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.231+517G>C		intron	N/A	ENSP00000364709.3
	F10	ENST00000375551.7	TSL:1	c.231+517G>C		intron	N/A	ENSP00000364701.3
	F10	ENST00000410083.6	TSL:1	n.231+517G>C		intron	N/A	ENSP00000386320.2

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

African (AFR) AF: 0.479 AC: 358 AN: 748

American (AMR) AF: 0.533 AC: 1832 AN: 3440

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 613 AN: 814

East Asian (EAS) AF: 0.499 AC: 1314 AN: 2634

South Asian (SAS) AF: 0.689 AC: 3810 AN: 5526

European-Finnish (FIN) AF: 0.485 AC: 838 AN: 1728

Middle Eastern (MID) AF: 0.685 AC: 115 AN: 168

European-Non Finnish (NFE) AF: 0.597 AC: 15781 AN: 26428

Other (OTH) AF: 0.590 AC: 1378 AN: 2334

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

African (AFR) AF: 0.495 AC: 19395 AN: 39184

American (AMR) AF: 0.572 AC: 8685 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2625 AN: 3470

East Asian (EAS) AF: 0.518 AC: 2660 AN: 5136

South Asian (SAS) AF: 0.672 AC: 3243 AN: 4824

European-Finnish (FIN) AF: 0.511 AC: 5413 AN: 10592

Middle Eastern (MID) AF: 0.655 AC: 190 AN: 290

European-Non Finnish (NFE) AF: 0.619 AC: 42036 AN: 67904

Other (OTH) AF: 0.589 AC: 1228 AN: 2086

Alfa AF: 0.454 Hom.: 1257

Bravo AF: 0.570

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.73
DANN	Benign	0.45
PhyloP100		-2.6
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: rs693335; hg19: chr13-113784443;