rs1555794302

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_015629.4(PRPF31):​c.1129delC​(p.Arg377ValfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. R377R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 28)

Consequence

PRPF31
NM_015629.4 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.91

Publications

1 publications found
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]
PRPF31 Gene-Disease associations (from GenCC):
  • PRPF31-related retinopathy
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • retinitis pigmentosa 11
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
  • retinitis pigmentosa
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 11 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-54128358-AC-A is Pathogenic according to our data. Variant chr19-54128358-AC-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 438043.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PRPF31NM_015629.4 linkc.1129delC p.Arg377ValfsTer2 frameshift_variant Exon 11 of 14 ENST00000321030.9 NP_056444.3 Q8WWY3-1
PRPF31XM_006723137.5 linkc.1129delC p.Arg377ValfsTer2 frameshift_variant Exon 11 of 14 XP_006723200.1 Q8WWY3-1
PRPF31XM_047438587.1 linkc.*264delC downstream_gene_variant XP_047294543.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PRPF31ENST00000321030.9 linkc.1129delC p.Arg377ValfsTer2 frameshift_variant Exon 11 of 14 1 NM_015629.4 ENSP00000324122.4 Q8WWY3-1

Frequencies

GnomAD3 genomes
Cov.:
28
GnomAD4 exome
Cov.:
43
GnomAD4 genome
Cov.:
28

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Retinitis pigmentosa Pathogenic:1
Jan 01, 2015
NIHR Bioresource Rare Diseases, University of Cambridge
Significance:Likely pathogenic
Review Status:no assertion criteria provided
Collection Method:research

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
2.9
Mutation Taster
=0/200
disease causing (ClinVar)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.20
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.20
Position offset: 2

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

Publications

Other links and lift over

dbSNP: rs1555794302; hg19: chr19-54631733; API