4-186285811-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3PP5_Moderate
The NM_000128.4(F11):c.1478C>T(p.Thr493Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000233 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T493R) has been classified as Uncertain significance.
Frequency
Consequence
NM_000128.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F11 | NM_000128.4 | c.1478C>T | p.Thr493Ile | missense_variant, splice_region_variant | 12/15 | ENST00000403665.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F11 | ENST00000403665.7 | c.1478C>T | p.Thr493Ile | missense_variant, splice_region_variant | 12/15 | 1 | NM_000128.4 | P1 | |
F11 | ENST00000264691.4 | c.176C>T | p.Thr59Ile | missense_variant, splice_region_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461830Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 727222
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary factor XI deficiency disease Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Apr 21, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at