rs864309498
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001346413.3(PCF11):c.3618delT(p.Phe1206fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
PCF11
NM_001346413.3 frameshift
NM_001346413.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.44
Genes affected
PCF11 (HGNC:30097): (PCF11 cleavage and polyadenylation factor subunit) The protein encoded by this gene binds to CLP1 to form pre-mRNA cleavage factor IIm. The encoded protein is necessary for efficient Pol II transcription termination and may be involved in degradation of the 3' product of polyA site cleavage. [provided by RefSeq, Oct 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCF11 | NM_001346413.3 | c.3618delT | p.Phe1206fs | frameshift_variant | 8/16 | ENST00000690938.1 | NP_001333342.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCF11 | ENST00000690938.1 | c.3618delT | p.Phe1206fs | frameshift_variant | 8/16 | NM_001346413.3 | ENSP00000508500.1 | |||
PCF11 | ENST00000298281.8 | c.3225delT | p.Phe1075fs | frameshift_variant | 8/16 | 1 | ENSP00000298281.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Acute megakaryoblastic leukemia;C1334655:Mediastinal germ cell tumor Uncertain:1
Uncertain significance, no assertion criteria provided | research | McDonnell Genome Institute, Washington University in St. Louis | Oct 22, 2015 | - - |
Computational scores
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Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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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