GeneBe

rs1555791188

Variant names:

Variant summary

Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate

The NM_015629.4(PRPF31):​c.1A>G​(p.Met1?) variant causes a start lost 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. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PRPF31
NM_015629.4 start_lost

Scores

8
6
2

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 8.01
Variant links:
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, next in-frame start position is after 11 pathogenic variants. Next in-frame start position is after 59 codons. Genomic position: 54118453. Lost 0.117 part of the original CDS.
PS1
Another start lost variant in NM_015629.4 (PRPF31) was described as [Likely_pathogenic] in Lovd
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-54118279-A-G is Pathogenic according to our data. Variant chr19-54118279-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 3235232.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRPF31NM_015629.4 linkc.1A>G p.Met1? start_lost Exon 2 of 14 ENST00000321030.9 NP_056444.3 Q8WWY3-1
PRPF31XM_006723137.5 linkc.1A>G p.Met1? start_lost Exon 2 of 14 XP_006723200.1 Q8WWY3-1
PRPF31XM_047438587.1 linkc.1A>G p.Met1? start_lost Exon 2 of 10 XP_047294543.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRPF31ENST00000321030.9 linkc.1A>G p.Met1? start_lost Exon 2 of 14 1 NM_015629.4 ENSP00000324122.4 Q8WWY3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Retinitis pigmentosa 11 Pathogenic:1
Nov 03, 2021
MVZ Medizinische Genetik Mainz
Significance: Pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

ACMG Criteria: PVS1, PM5, PM2_SUP, PP4 (ACMG Version 3) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.48
D
BayesDel_noAF
Pathogenic
0.45
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.59
.;D;T;.;T;.
Eigen
Benign
0.075
Eigen_PC
Uncertain
0.22
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.90
.;.;D;D;D;D
M_CAP
Pathogenic
0.95
D
MetaRNN
Pathogenic
0.99
D;D;D;D;D;D
MetaSVM
Uncertain
0.19
D
PROVEAN
Uncertain
-3.3
D;D;D;D;D;D
REVEL
Pathogenic
0.82
Sift
Pathogenic
0.0
D;D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D
Polyphen
0.0010
.;B;.;.;.;.
Vest4
0.93
MutPred
0.97
Loss of solvent accessibility (P = 0.3103);Loss of solvent accessibility (P = 0.3103);Loss of solvent accessibility (P = 0.3103);Loss of solvent accessibility (P = 0.3103);Loss of solvent accessibility (P = 0.3103);Loss of solvent accessibility (P = 0.3103);
MVP
0.98
ClinPred
0.99
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.82
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-54621659; API