rs1555794509

Variant names:

• chr19-54128903-CAGGCCTCAGCCGGGCCGAGTGGGTACCGGAGCAGGTGCCCGTGGGACCGGCCGGCTGGTGACCGCTGGGCTTCGGGCTGGTGGAGGGGGTGCCTCGGTGGCTGGAGGGCAGGGCCTGGTCGCTGAACTGCAGGGCGCCTCCTCTCCCCCCTAGATCGAGGAGGACGCCTACCAGGAGGACCTGGGATTCAGCCTGGGCCACCT-C
• rs1555794509
• NM_015629.4:c.1147-153_1196del

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_015629.4(PRPF31):​c.1147-153_1196del​(p.Ile383fs) variant causes a frameshift, splice acceptor, splice region, intron 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). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PRPF31 NM_015629.4 frameshift, splice_acceptor, splice_region, intron
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.420

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]

ACMG classification

Verdict is Pathogenic. Variant got 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 19-54128903-CAGGCCTCAGCCGGGCCGAGTGGGTACCGGAGCAGGTGCCCGTGGGACCGGCCGGCTGGTGACCGCTGGGCTTCGGGCTGGTGGAGGGGGTGCCTCGGTGGCTGGAGGGCAGGGCCTGGTCGCTGAACTGCAGGGCGCCTCCTCTCCCCCCTAGATCGAGGAGGACGCCTACCAGGAGGACCTGGGATTCAGCCTGGGCCACCT-C is Pathogenic according to our data. Variant chr19-54128903-CAGGCCTCAGCCGGGCCGAGTGGGTACCGGAGCAGGTGCCCGTGGGACCGGCCGGCTGGTGACCGCTGGGCTTCGGGCTGGTGGAGGGGGTGCCTCGGTGGCTGGAGGGCAGGGCCTGGTCGCTGAACTGCAGGGCGCCTCCTCTCCCCCCTAGATCGAGGAGGACGCCTACCAGGAGGACCTGGGATTCAGCCTGGGCCACCT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 438251.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.1147-153_1196del	p.Ile383fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	Exon 12 of 14	ENST00000321030.9	NP_056444.3
PRPF31	XM_006723137.5	c.1147-153_1196del	p.Ile383fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	Exon 12 of 14		XP_006723200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9	c.1147-153_1196del	p.Ile383fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	Exon 12 of 14	1	NM_015629.4	ENSP00000324122.4
PRPF31	ENST00000391755.1	c.1129-153_1178del	p.Ile377fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	Exon 11 of 13	5		ENSP00000375635.1
PRPF31	ENST00000419967.5	c.1147-153_1196del	p.Ile383fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	Exon 12 of 13	5		ENSP00000405166.2
PRPF31	ENST00000466404.5	n.1121-153_1170del		splice_acceptor_variant, splice_region_variant, intron_variant, non_coding_transcript_exon_variant	Exon 10 of 11	2

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Retinitis pigmentosa Pathogenic:1

-

NIHR Bioresource Rare Diseases, University of Cambridge

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555794509; hg19: chr19-54632278;