19-54118301-T-G
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_015629.4(PRPF31):c.23T>G(p.Leu8Ter) variant causes a stop gained 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 Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
PRPF31
NM_015629.4 stop_gained
NM_015629.4 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 6.97
Genes affected
PRPF31 (HGNC:15446): (pre-mRNA processing factor 31) This gene encodes a component of the spliceosome complex and is one of several retinitis pigmentosa-causing genes. When the gene product is added to the spliceosome complex, activation occurs.[provided by RefSeq, Jan 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 86 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-54118301-T-G is Pathogenic according to our data. Variant chr19-54118301-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 1351673.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRPF31 | NM_015629.4 | c.23T>G | p.Leu8Ter | stop_gained | 2/14 | ENST00000321030.9 | NP_056444.3 | |
PRPF31-AS1 | XR_007067340.1 | n.1843-622A>C | intron_variant, non_coding_transcript_variant | |||||
PRPF31 | XM_006723137.5 | c.23T>G | p.Leu8Ter | stop_gained | 2/14 | XP_006723200.1 | ||
PRPF31 | XM_047438587.1 | c.23T>G | p.Leu8Ter | stop_gained | 2/10 | XP_047294543.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRPF31 | ENST00000321030.9 | c.23T>G | p.Leu8Ter | stop_gained | 2/14 | 1 | NM_015629.4 | ENSP00000324122 | P1 |
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: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 03, 2021 | For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PRPF31-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu8*) in the PRPF31 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PRPF31 are known to be pathogenic (PMID: 18317597, 23950152). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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
Publications
No publications associated with this variant yet.