rs748139184
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_000128.4(F11):c.484C>T(p.Arg162Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,614,048 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 Uncertain significance (★★).
Frequency
Consequence
NM_000128.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F11 | NM_000128.4 | c.484C>T | p.Arg162Cys | missense_variant, splice_region_variant | 5/15 | ENST00000403665.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F11 | ENST00000403665.7 | c.484C>T | p.Arg162Cys | missense_variant, splice_region_variant | 5/15 | 1 | NM_000128.4 | P1 | |
F11 | ENST00000492972.6 | c.484C>T | p.Arg162Trp | missense_variant | 5/5 | 2 | |||
F11 | ENST00000514715.1 | n.356C>T | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251330Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135842
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461874Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727244
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74334
ClinVar
Submissions by phenotype
Hereditary factor XI deficiency disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jul 31, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 06, 2018 | The R162C variant in the F11 gene has been reported previously as a pathogenic variant, denoted as R144C due to alternative nomenclature, showing this variant introduces a cysteine which may disrupt disulphide bridge formation (Saunders et al., 2009). The R162C variant is observed in 7/33572 (0.02%) alleles from individuals of Latino background, in large population cohorts (Lek et al., 2016). The R162C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret R162C as a variant of uncertain significance. - |
Plasma factor XI deficiency Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 30, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at