chr19-54121859-G-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1_ModeratePM2PP5_Very_Strong
The NM_015629.4(PRPF31):c.239-1G>A variant causes a splice acceptor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_015629.4 splice_acceptor, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRPF31 | NM_015629.4 | c.239-1G>A | splice_acceptor_variant, intron_variant | Intron 3 of 13 | ENST00000321030.9 | NP_056444.3 | ||
PRPF31 | XM_006723137.5 | c.239-1G>A | splice_acceptor_variant, intron_variant | Intron 3 of 13 | XP_006723200.1 | |||
PRPF31 | XM_047438587.1 | c.239-1G>A | splice_acceptor_variant, intron_variant | Intron 3 of 9 | XP_047294543.1 | |||
PRPF31-AS1 | NR_186329.1 | n.552C>T | non_coding_transcript_exon_variant | Exon 3 of 4 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Retinitis pigmentosa 11 Pathogenic:1
The PRPF31 c.239-1G>A 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: PVS1, PM2. Based on this evidence we have classified this variant as Likely Pathogenic. -
not provided Pathogenic:1
This sequence change affects an acceptor splice site in intron 3 of the PRPF31 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PRPF31 are known to be pathogenic (PMID: 18317597, 23950152). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with inherited retinal dystrophy (PMID: 33090715; Invitae). ClinVar contains an entry for this variant (Variation ID: 866371). 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
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at