rs587776590
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 8P and 5B. PP5_Very_StrongBP4BS2
The NM_015629.4(PRPF31):c.527+3A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_015629.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRPF31 | NM_015629.4 | c.527+3A>G | splice_region_variant, intron_variant | ENST00000321030.9 | NP_056444.3 | |||
PRPF31 | XM_006723137.5 | c.527+3A>G | splice_region_variant, intron_variant | XP_006723200.1 | ||||
PRPF31 | XM_047438587.1 | c.527+3A>G | splice_region_variant, intron_variant | XP_047294543.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRPF31 | ENST00000321030.9 | c.527+3A>G | splice_region_variant, intron_variant | 1 | NM_015629.4 | ENSP00000324122.4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461394Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727030
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Retinitis pigmentosa 11 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 2007 | - - |
Likely pathogenic, criteria provided, single submitter | research | Ocular Genomics Institute, Massachusetts Eye and Ear | Apr 08, 2021 | The PRPF31 c.527+3A>G variant was identified in an individual with retinitis pigmentosa with a presumed dominant inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2, PP3, PP1-S. Based on this evidence we have classified this variant as Likely pathogenic. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 23, 2024 | This sequence change falls in intron 6 of the PRPF31 gene. It does not directly change the encoded amino acid sequence of the PRPF31 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with autosomal dominant retinitis pigmentosa (PMID: 11545739, 29957067, 30582903). It has also been observed to segregate with disease in related individuals. This variant is also known as IVS6+3A>G. ClinVar contains an entry for this variant (Variation ID: 4360). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Retinal dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Jan 13, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at