rs5962
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000504.4(F10):c.399C>T(p.Asn133=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,614,112 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.017 ( 63 hom., cov: 32)
Exomes 𝑓: 0.0023 ( 72 hom. )
Consequence
F10
NM_000504.4 synonymous
NM_000504.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.79
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
Variant 13-113140947-C-T is Benign according to our data. Variant chr13-113140947-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 311274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.79 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F10 | NM_000504.4 | c.399C>T | p.Asn133= | synonymous_variant | 5/8 | ENST00000375559.8 | |
F10 | NM_001312675.2 | c.399C>T | p.Asn133= | synonymous_variant | 5/8 | ||
F10 | NM_001312674.2 | c.370+1477C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F10 | ENST00000375559.8 | c.399C>T | p.Asn133= | synonymous_variant | 5/8 | 1 | NM_000504.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0170 AC: 2586AN: 152230Hom.: 64 Cov.: 32
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GnomAD3 exomes AF: 0.00496 AC: 1247AN: 251294Hom.: 33 AF XY: 0.00387 AC XY: 526AN XY: 135892
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GnomAD4 exome AF: 0.00233 AC: 3403AN: 1461764Hom.: 72 Cov.: 31 AF XY: 0.00214 AC XY: 1556AN XY: 727186
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GnomAD4 genome ? AF: 0.0170 AC: 2589AN: 152348Hom.: 63 Cov.: 32 AF XY: 0.0164 AC XY: 1221AN XY: 74490
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary factor X deficiency disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at