rs121965066
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000128.4(F11):c.438C>A(p.Cys146Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 1,614,102 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000128.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F11 | NM_000128.4 | c.438C>A | p.Cys146Ter | stop_gained | 5/15 | ENST00000403665.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F11 | ENST00000403665.7 | c.438C>A | p.Cys146Ter | stop_gained | 5/15 | 1 | NM_000128.4 | P1 | |
F11 | ENST00000492972.6 | c.438C>A | p.Cys146Ter | stop_gained | 5/5 | 2 | |||
F11 | ENST00000514715.1 | n.310C>A | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251302Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135802
GnomAD4 exome AF: 0.000254 AC: 371AN: 1461890Hom.: 1 Cov.: 31 AF XY: 0.000232 AC XY: 169AN XY: 727246
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74354
ClinVar
Submissions by phenotype
Hereditary factor XI deficiency disease Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 06, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 28, 2022 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2004 | - - |
Likely pathogenic, criteria provided, single submitter | research | NIHR Bioresource Rare Diseases, University of Cambridge | Feb 01, 2019 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2023 | This sequence change creates a premature translational stop signal (p.Cys146*) in the F11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in F11 are known to be pathogenic (PMID: 23929304). This variant is present in population databases (rs121965066, gnomAD 0.009%). This premature translational stop signal has been observed in individuals with autosomal recessive factor XI deficiency (PMID: 7669672, 16835901). This variant is also known as p.Cys128*. ClinVar contains an entry for this variant (Variation ID: 11896). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Nov 02, 2023 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Also reported as C128X due to the use of alternate nomenclature; This variant is associated with the following publications: (PMID: 15180874, 7669672, 16835901, 31064749, 19652879) - |
Plasma factor XI deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 28, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at