rs773905328
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000128.4(F11):c.1107C>A(p.Tyr369Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Y369Y) has been classified as Likely benign. 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.1107C>A | p.Tyr369Ter | stop_gained | 10/15 | ENST00000403665.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F11 | ENST00000403665.7 | c.1107C>A | p.Tyr369Ter | stop_gained | 10/15 | 1 | NM_000128.4 | P1 | |
F11 | ENST00000452239.1 | c.555C>A | p.Tyr185Ter | stop_gained | 5/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152122Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251352Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135846
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461638Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727132
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152122Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74306
ClinVar
Submissions by phenotype
Hereditary factor XI deficiency disease Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 12, 2022 | - - |
Likely pathogenic, criteria provided, single submitter | literature only | Counsyl | Jan 06, 2015 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | This sequence change creates a premature translational stop signal (p.Tyr369*) 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 (rs773905328, gnomAD 0.04%). This premature translational stop signal has been observed in individual(s) with clinical features of autosomal recessive factor XI deficiency (PMID: 14508802, 25681615, 32220196). This variant is also known as Tyr351-->Term and p.Tyr351X. ClinVar contains an entry for this variant (Variation ID: 189115). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at