19-54118301-T-G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_015629.4(PRPF31):​c.23T>G​(p.Leu8Ter) variant causes a stop gained 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 (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PRPF31
NM_015629.4 stop_gained

Scores

5
1
1

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 6.97
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 86 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-54118301-T-G is Pathogenic according to our data. Variant chr19-54118301-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 1351673.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PRPF31NM_015629.4 linkuse as main transcriptc.23T>G p.Leu8Ter stop_gained 2/14 ENST00000321030.9 NP_056444.3
PRPF31-AS1XR_007067340.1 linkuse as main transcriptn.1843-622A>C intron_variant, non_coding_transcript_variant
PRPF31XM_006723137.5 linkuse as main transcriptc.23T>G p.Leu8Ter stop_gained 2/14 XP_006723200.1
PRPF31XM_047438587.1 linkuse as main transcriptc.23T>G p.Leu8Ter stop_gained 2/10 XP_047294543.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PRPF31ENST00000321030.9 linkuse as main transcriptc.23T>G p.Leu8Ter stop_gained 2/141 NM_015629.4 ENSP00000324122 P1Q8WWY3-1

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

not provided Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 03, 2021For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PRPF31-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu8*) in the PRPF31 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PRPF31 are known to be pathogenic (PMID: 18317597, 23950152). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.62
D
BayesDel_noAF
Pathogenic
0.63
CADD
Pathogenic
39
DANN
Uncertain
0.99
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.97
D
MutationTaster
Benign
1.0
A;A;A
Vest4
0.80
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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: chr19-54621681; API