chr11-83166591-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001346413.3(PCF11):c.1694G>A(p.Arg565Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
PCF11
NM_001346413.3 missense
NM_001346413.3 missense
Scores
6
4
9
Clinical Significance
Conservation
PhyloP100: 9.02
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.32156223).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PCF11 | NM_001346413.3 | c.1694G>A | p.Arg565Gln | missense_variant | 5/16 | ENST00000690938.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCF11 | ENST00000690938.1 | c.1694G>A | p.Arg565Gln | missense_variant | 5/16 | NM_001346413.3 | P3 | ||
PCF11 | ENST00000298281.8 | c.1694G>A | p.Arg565Gln | missense_variant | 5/16 | 1 | A1 | ||
PCF11 | ENST00000530304.5 | c.1694G>A | p.Arg565Gln | missense_variant | 5/8 | 1 | |||
PCF11 | ENST00000530660.5 | c.1694G>A | p.Arg565Gln | missense_variant | 5/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151956Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248470Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134944
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461602Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727094
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GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151956Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74198
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 16, 2024 | The c.1694G>A (p.R565Q) alteration is located in exon 5 (coding exon 5) of the PCF11 gene. This alteration results from a G to A substitution at nucleotide position 1694, causing the arginine (R) at amino acid position 565 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Pathogenic
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0554);Loss of MoRF binding (P = 0.0554);Loss of MoRF binding (P = 0.0554);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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