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). Synonymous variant affecting the same amino acid position (i.e. I383I) has been classified as Likely benign. 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;