chr19-54122530-CAA-C

Position:

• chr19-54122530-CAA-C

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1 PM2 PP5_Very_Strong

The NM_015629.4(PRPF31):​c.358_359del​(p.Lys120GlufsTer4) variant causes a frameshift change involving the alteration of a conserved nucleotide. 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, multiple submitters, no conflicts P:2
• Conservation: PhyloP100: 8.23

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 18 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 19-54122530-CAA-C is Pathogenic according to our data. Variant chr19-54122530-CAA-C is described in ClinVar as [Pathogenic]. Clinvar id is 1275773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-54122530-CAA-C is described in Lovd as [Pathogenic]. Variant chr19-54122530-CAA-C is described in Lovd as [Likely_pathogenic]. Variant chr19-54122530-CAA-C is described in Lovd as [Pathogenic]. Variant chr19-54122530-CAA-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF31	NM_015629.4	c.358_359del	p.Lys120GlufsTer4	frameshift_variant	5/14	ENST00000321030.9	NP_056444.3
PRPF31-AS1	XR_007067340.1	n.1146_1147del		non_coding_transcript_exon_variant	2/3
PRPF31	XM_006723137.5	c.358_359del	p.Lys120GlufsTer4	frameshift_variant	5/14		XP_006723200.1
PRPF31	XM_047438587.1	c.358_359del	p.Lys120GlufsTer4	frameshift_variant	5/10		XP_047294543.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9	c.358_359del	p.Lys120GlufsTer4	frameshift_variant	5/14	1	NM_015629.4	ENSP00000324122	P1
PRPF31-AS1	ENST00000452097.1	n.2812_2813del		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 04, 2022	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1275773). This premature translational stop signal has been observed in individual(s) with retinitis pigmentosa (PMID: 32100970). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys120Glufs*4) 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). -
Pathogenic, criteria provided, single submitter	clinical testing	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	Sep 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr19-54625909;