rs1555791188
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP3PP5
The NM_015629.4(PRPF31):c.1A>T(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
PRPF31
NM_015629.4 start_lost
NM_015629.4 start_lost
Scores
8
3
3
Clinical Significance
Conservation
PhyloP100: 8.01
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 14 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_015629.4 (PRPF31) was described as [Likely_pathogenic] in ClinVar as 804151
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 19-54118279-A-T is Pathogenic according to our data. Variant chr19-54118279-A-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 438044.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-54118279-A-T is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRPF31 | NM_015629.4 | c.1A>T | p.Met1? | start_lost | 2/14 | ENST00000321030.9 | |
PRPF31-AS1 | XR_007067340.1 | n.1843-600T>A | intron_variant, non_coding_transcript_variant | ||||
PRPF31 | XM_006723137.5 | c.1A>T | p.Met1? | start_lost | 2/14 | ||
PRPF31 | XM_047438587.1 | c.1A>T | p.Met1? | start_lost | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRPF31 | ENST00000321030.9 | c.1A>T | p.Met1? | start_lost | 2/14 | 1 | NM_015629.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460676Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726646
GnomAD4 exome
AF:
AC:
1
AN:
1460676
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
726646
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Retinitis pigmentosa Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Benign
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D
PROVEAN
Uncertain
D;D;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D
Polyphen
0.0010
.;B;.;.;.;.
Vest4
MutPred
Loss of solvent accessibility (P = 0.5485);Loss of solvent accessibility (P = 0.5485);Loss of solvent accessibility (P = 0.5485);Loss of solvent accessibility (P = 0.5485);Loss of solvent accessibility (P = 0.5485);Loss of solvent accessibility (P = 0.5485);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 13
Find out detailed SpliceAI scores and Pangolin per-transcript scores at