chr19-54121883-C-CCTGAATACCGCGT

Variant names:

• chr19-54121883-C-CCTGAATACCGCGT
• NM_015629.4:c.264_276dupTGAATACCGCGTC

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_015629.4(PRPF31):​c.264_276dupTGAATACCGCGTC​(p.Ile93fs) variant causes a frameshift, stop gained change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRPF31 NM_015629.4 frameshift, stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 6.85

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-AS1 (HGNC:40700): (PRPF31 antisense RNA 1)

ACMG classification

Verdict is Pathogenic. Variant got 12 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 19-54121883-C-CCTGAATACCGCGT is Pathogenic according to our data. Variant chr19-54121883-C-CCTGAATACCGCGT is described in ClinVar as [Pathogenic]. Clinvar id is 2092562.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.264_276dupTGAATACCGCGTC	p.Ile93fs	frameshift_variant, stop_gained	Exon 4 of 14	ENST00000321030.9	NP_056444.3
PRPF31	XM_006723137.5	c.264_276dupTGAATACCGCGTC	p.Ile93fs	frameshift_variant, stop_gained	Exon 4 of 14		XP_006723200.1
PRPF31	XM_047438587.1	c.264_276dupTGAATACCGCGTC	p.Ile93fs	frameshift_variant, stop_gained	Exon 4 of 10		XP_047294543.1
PRPF31-AS1	NR_186329.1	n.515_527dupACGCGGTATTCAG		non_coding_transcript_exon_variant	Exon 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9	c.264_276dupTGAATACCGCGTC	p.Ile93fs	frameshift_variant, stop_gained	Exon 4 of 14	1	NM_015629.4	ENSP00000324122.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

May 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change creates a premature translational stop signal (p.Ile93*) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PRPF31-related conditions. ClinVar contains an entry for this variant (Variation ID: 2092562). For these reasons, this variant has been classified as Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr19-54625262;