17-1650774-GAGGCTGAAGCAGGAGGCAGGGAAACGGTCAGGC-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006445.4(PRPF8):c.7003_*27del variant causes a stop lost, 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A2335A) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Consequence
PRPF8
NM_006445.4 stop_lost, 3_prime_UTR
NM_006445.4 stop_lost, 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.39
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRPF8 | NM_006445.4 | c.7003_*27del | stop_lost, 3_prime_UTR_variant | 43/43 | ENST00000304992.11 | ||
PRPF8 | XM_024450537.2 | c.7003_*27del | stop_lost, 3_prime_UTR_variant | 43/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRPF8 | ENST00000304992.11 | c.7003_*27del | stop_lost, 3_prime_UTR_variant | 43/43 | 1 | NM_006445.4 | P1 |
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: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 03, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with PRPF8-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.7003_*27del, is a complex sequence change that results in the deletion of 1 and insertion of 31 amino acid(s) in the PRPF8 protein (p.Ala2335delins31). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.