rs1555792415
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_015629.4(PRPF31):c.358_359del(p.Lys120GlufsTer4) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
PRPF31
NM_015629.4 frameshift
NM_015629.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.23
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 18 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;
PP5
?
Variant 19-54122530-CAA-C is Pathogenic according to our data. Variant chr19-54122530-CAA-C is described in ClinVar as [Pathogenic]. Clinvar id is 1275773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-54122530-CAA-C is described in Lovd as [Pathogenic]. Variant chr19-54122530-CAA-C is described in Lovd as [Likely_pathogenic]. Variant chr19-54122530-CAA-C is described in Lovd as [Pathogenic]. Variant chr19-54122530-CAA-C is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRPF31 | NM_015629.4 | c.358_359del | p.Lys120GlufsTer4 | frameshift_variant | 5/14 | ENST00000321030.9 | |
PRPF31-AS1 | XR_007067340.1 | n.1146_1147del | non_coding_transcript_exon_variant | 2/3 | |||
PRPF31 | XM_006723137.5 | c.358_359del | p.Lys120GlufsTer4 | frameshift_variant | 5/14 | ||
PRPF31 | XM_047438587.1 | c.358_359del | p.Lys120GlufsTer4 | frameshift_variant | 5/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRPF31 | ENST00000321030.9 | c.358_359del | p.Lys120GlufsTer4 | frameshift_variant | 5/14 | 1 | NM_015629.4 | P1 | |
PRPF31-AS1 | ENST00000452097.1 | n.2812_2813del | non_coding_transcript_exon_variant | 1/4 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 04, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1275773). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 32100970). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys120Glufs*4) 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). - |
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen | Sep 15, 2021 | - - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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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.