rs1555794302

Positions:

• chr19-54128358-AC-A

Variant summary

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

The NM_015629.4(PRPF31):​c.1129del​(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). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 28)
• Consequence: PRPF31 NM_015629.4 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.91

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 19-54128358-AC-A is Pathogenic according to our data. Variant chr19-54128358-AC-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 438043.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-54128358-AC-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRPF31	NM_015629.4	c.1129del	p.Arg377ValfsTer2	frameshift_variant	11/14	ENST00000321030.9
PRPF31	XM_006723137.5	c.1129del	p.Arg377ValfsTer2	frameshift_variant	11/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF31	ENST00000321030.9	c.1129del	p.Arg377ValfsTer2	frameshift_variant	11/14	1	NM_015629.4	P1
PRPF31	ENST00000391755.1	c.1111del	p.Arg371ValfsTer2	frameshift_variant	10/13	5
PRPF31	ENST00000419967.5	c.1129del	p.Arg377ValfsTer2	frameshift_variant	11/13	5
PRPF31	ENST00000466404.5	n.1103del		non_coding_transcript_exon_variant	9/11	2

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

Submissions by phenotype

Retinitis pigmentosa Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

NIHR Bioresource Rare Diseases, University of Cambridge

Jan 01, 2015

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Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs1555794302; hg19: chr19-54631733;