19-54123867-G-C
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PM2PM5PP3_StrongPP5
The NM_015629.4(PRPF31):c.646G>C(p.Ala216Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A216T) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 33)
Consequence
PRPF31
NM_015629.4 missense
NM_015629.4 missense
Scores
15
3
1
Clinical Significance
Conservation
PhyloP100: 5.86
Publications
39 publications found
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 was made for transcript
Our verdict: Likely_pathogenic. The variant received 9 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr19-54123867-G-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3248916.Status of the report is no_assertion_criteria_provided, 0 stars.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.993
PP5
Variant 19-54123867-G-C is Pathogenic according to our data. Variant chr19-54123867-G-C is described in ClinVar as Pathogenic. ClinVar VariationId is 4359.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PRPF31 | NM_015629.4 | c.646G>C | p.Ala216Pro | missense_variant | Exon 7 of 14 | ENST00000321030.9 | NP_056444.3 | |
| PRPF31 | XM_006723137.5 | c.646G>C | p.Ala216Pro | missense_variant | Exon 7 of 14 | XP_006723200.1 | ||
| PRPF31 | XM_047438587.1 | c.646G>C | p.Ala216Pro | missense_variant | Exon 7 of 10 | XP_047294543.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Retinitis pigmentosa 11 Pathogenic:1
Jun 01, 2009
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
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Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
.;D;T;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;.;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H;.;.;.;.
PhyloP100
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D;D;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
1.0
.;D;.;.;.;.
Vest4
MutPred
Gain of catalytic residue at A216 (P = 0.0357);Gain of catalytic residue at A216 (P = 0.0357);Gain of catalytic residue at A216 (P = 0.0357);Gain of catalytic residue at A216 (P = 0.0357);Gain of catalytic residue at A216 (P = 0.0357);Gain of catalytic residue at A216 (P = 0.0357);
MVP
MPC
2.2
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
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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