chr17-1650819-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP2PP3_ModeratePP5
The NM_006445.4(PRPF8):c.6991G>A(p.Glu2331Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PRPF8
NM_006445.4 missense
NM_006445.4 missense
Scores
11
6
1
Clinical Significance
Conservation
PhyloP100: 5.92
Genes affected
PRPF8 (HGNC:17340): (pre-mRNA processing factor 8) Pre-mRNA splicing occurs in 2 sequential transesterification steps. The protein encoded by this gene is a component of both U2- and U12-dependent spliceosomes, and found to be essential for the catalytic step II in pre-mRNA splicing process. It contains several WD repeats, which function in protein-protein interactions. This protein has a sequence similarity to yeast Prp8 protein. This gene is a candidate gene for autosomal dominant retinitis pigmentosa. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
?
In a region_of_interest Required for interaction with EFTUD2 and SNRNP200 (size 34) in uniprot entity PRP8_HUMAN there are 50 pathogenic changes around while only 0 benign (100%) in NM_006445.4
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, PRPF8
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.869
PP5
?
Variant 17-1650819-C-T is Pathogenic according to our data. Variant chr17-1650819-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 803296.We mark this variant Likely_pathogenic, oryginal submissions are: {Likely_pathogenic=1, Uncertain_significance=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRPF8 | NM_006445.4 | c.6991G>A | p.Glu2331Lys | missense_variant | 43/43 | ENST00000304992.11 | |
PRPF8 | XM_024450537.2 | c.6991G>A | p.Glu2331Lys | missense_variant | 43/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRPF8 | ENST00000304992.11 | c.6991G>A | p.Glu2331Lys | missense_variant | 43/43 | 1 | NM_006445.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1461838Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727214
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1461838
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
727214
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 NFE exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Retinitis pigmentosa 13 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Retinal dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Dept Of Ophthalmology, Nagoya University | Oct 01, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Pathogenic
D;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
N;.
REVEL
Pathogenic
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Polyphen
P;P
Vest4
MutPred
Gain of ubiquitination at E2331 (P = 0.006);Gain of ubiquitination at E2331 (P = 0.006);
MVP
MPC
0.78
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at