chr19-54121883-C-CCTGAATACCGCGT

Position:

• chr19-54121883-C-CCTGAATACCGCGT

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_276dup​(p.Ile93Ter) variant causes a frameshift 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
• 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/exons	MANE	UniProt
PRPF31	NM_015629.4	c.264_276dup	p.Ile93Ter	frameshift_variant	4/14	ENST00000321030.9
PRPF31-AS1	XR_007067340.1	n.1794_1795insACGCGGTATTCAG		non_coding_transcript_exon_variant	2/3
PRPF31	XM_006723137.5	c.264_276dup	p.Ile93Ter	frameshift_variant	4/14
PRPF31	XM_047438587.1	c.264_276dup	p.Ile93Ter	frameshift_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF31	ENST00000321030.9	c.264_276dup	p.Ile93Ter	frameshift_variant	4/14	1	NM_015629.4	P1
PRPF31-AS1	ENST00000452097.1	n.3228_3229insACGCGGTATTCAG		non_coding_transcript_exon_variant	3/4	2

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

Pathogenic, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 03, 2022

For 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.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). -

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;