13-113129564-CT-TTGCTCATACGAAGAGGCCC

Position:

• chr13-113129564-CT-TTGCTCATACGAAGAGGCCC

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PM4 PP3 PP5_Moderate

The NM_000504.4(F10):​c.183_184delCTinsTTGCTCATACGAAGAGGCCC​(p.Cys62_Ser63insSerTyrGluGluAlaArg) variant causes a conservative inframe insertion, synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: F10 NM_000504.4 conservative_inframe_insertion, synonymous
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.86

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

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000504.4.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 13-113129564-CT-TTGCTCATACGAAGAGGCCC is Pathogenic according to our data. Variant chr13-113129564-CT-TTGCTCATACGAAGAGGCCC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3575773.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F10	NM_000504.4	c.183_184delCTinsTTGCTCATACGAAGAGGCCC	p.Cys62_Ser63insSerTyrGluGluAlaArg	conservative_inframe_insertion, synonymous_variant	2/8	ENST00000375559.8	NP_000495.1
F10	NM_001312674.2	c.183_184delCTinsTTGCTCATACGAAGAGGCCC	p.Cys62_Ser63insSerTyrGluGluAlaArg	conservative_inframe_insertion, synonymous_variant	2/7		NP_001299603.1
F10	NM_001312675.2	c.183_184delCTinsTTGCTCATACGAAGAGGCCC	p.Cys62_Ser63insSerTyrGluGluAlaArg	conservative_inframe_insertion, synonymous_variant	2/8		NP_001299604.1
F10-AS1	NR_126424.1	n.41+441_41+442delAGinsGGGCCTCTTCGTATGAGCAA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F10	ENST00000375559.8	c.183_184delCTinsTTGCTCATACGAAGAGGCCC	p.Cys62_Ser63insSerTyrGluGluAlaArg	conservative_inframe_insertion, synonymous_variant	2/8	1	NM_000504.4	ENSP00000364709.3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary factor X deficiency disease Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-113783878;