13-113129397-G-GGGAGCCTGGGTGAAGA

Position:

• chr13-113129397-G-GGGAGCCTGGGTGAAGA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000504.4(F10):​c.71-42_71-41insAGAGGAGCCTGGGTGA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,602,334 control chromosomes in the GnomAD database, including 16,619 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1420 hom., cov: 30)
  • Exomes 𝑓: 0.14 (15199 hom.)
• Consequence: F10 NM_000504.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.103

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:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 13-113129397-G-GGGAGCCTGGGTGAAGA is Benign according to our data. Variant chr13-113129397-G-GGGAGCCTGGGTGAAGA is described in ClinVar as [Benign]. Clinvar id is 1178123.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F10	NM_000504.4	c.71-42_71-41insAGAGGAGCCTGGGTGA		intron_variant		ENST00000375559.8
F10-AS1	NR_126424.1	n.42-521_42-520insTCTTCACCCAGGCTCC		intron_variant, non_coding_transcript_variant
F10	NM_001312674.2	c.71-42_71-41insAGAGGAGCCTGGGTGA		intron_variant
F10	NM_001312675.2	c.71-42_71-41insAGAGGAGCCTGGGTGA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F10	ENST00000375559.8	c.71-42_71-41insAGAGGAGCCTGGGTGA		intron_variant		1	NM_000504.4	P1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19755 AN: 151922 Hom.: 1420 Cov.: 30

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0135

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.148

GnomAD4 exome AF: 0.139 AC: 201455 AN: 1450296 Hom.: 15199 AF XY: 0.142 AC XY: 102882 AN XY: 722010

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.0898

Gnomad4 ASJ exome AF: 0.204

Gnomad4 EAS exome AF: 0.0187

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.130 AC: 19761 AN: 152038 Hom.: 1420 Cov.: 30 AF XY: 0.129 AC XY: 9612 AN XY: 74362

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.0135

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.146

Alfa AF: 0.128 Hom.: 88

Asia WGS AF: 0.104 AC: 360 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs45507496; hg19: chr13-113783711;