chr1-150325093-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004698.4(PRPF3):c.145+6T>C variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.0000031 in 1,612,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
PRPF3
NM_004698.4 splice_donor_region, intron
NM_004698.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.8281
2
Clinical Significance
Conservation
PhyloP100: 4.67
Genes affected
PRPF3 (HGNC:17348): (pre-mRNA processing factor 3) The removal of introns from nuclear pre-mRNAs occurs on complexes called spliceosomes, which are made up of 4 small nuclear ribonucleoprotein (snRNP) particles and an undefined number of transiently associated splicing factors. This gene product is one of several proteins that associate with U4 and U6 snRNPs. Mutations in this gene are associated with retinitis pigmentosa-18. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRPF3 | NM_004698.4 | c.145+6T>C | splice_donor_region_variant, intron_variant | ENST00000324862.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRPF3 | ENST00000324862.7 | c.145+6T>C | splice_donor_region_variant, intron_variant | 1 | NM_004698.4 | P1 | |||
PRPF3 | ENST00000496202.5 | n.307+6T>C | splice_donor_region_variant, intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251386Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135854
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460218Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 726474
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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 14, 2022 | ClinVar contains an entry for this variant (Variation ID: 1515163). 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. 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 is not likely to affect RNA splicing. This variant has not been reported in the literature in individuals affected with PRPF3-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change falls in intron 2 of the PRPF3 gene. It does not directly change the encoded amino acid sequence of the PRPF3 protein. It affects a nucleotide within the consensus splice site. - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at