rs1554671407

Positions:

• chr9-32541955-CT-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The ENST00000360538.7(TOPORS):​c.2569del​(p.Arg857GlyfsTer9) 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 (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TOPORS ENST00000360538.7 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.41

Genes affected

TOPORS (HGNC:21653): (TOP1 binding arginine/serine rich protein, E3 ubiquitin ligase) This gene encodes a nuclear protein which is serine and arginine rich, and contains a RING-type zinc finger domain. It is highly expressed in the testis, and functions as an ubiquitin-protein E3 ligase. Mutations in this gene are associated with retinitis pigmentosa type 31. Alternatively spliced transcript variants, encoding different isoforms, have been observed for this locus. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-32541955-CT-C is Pathogenic according to our data. Variant chr9-32541955-CT-C is described in ClinVar as [Pathogenic]. Clinvar id is 438067.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr9-32541955-CT-C is described in Lovd as [Pathogenic]. Variant chr9-32541955-CT-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOPORS	NM_005802.5	c.2569del	p.Arg857GlyfsTer9	frameshift_variant	3/3	ENST00000360538.7	NP_005793.2
TOPORS	NM_001195622.2	c.2374del	p.Arg792GlyfsTer9	frameshift_variant	2/2		NP_001182551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOPORS	ENST00000360538.7	c.2569del	p.Arg857GlyfsTer9	frameshift_variant	3/3	1	NM_005802.5	ENSP00000353735	P3
TOPORS	ENST00000379858.1	c.2374del	p.Arg792GlyfsTer9	frameshift_variant	2/2	1		ENSP00000369187	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Retinitis pigmentosa Pathogenic:1

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)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554671407; hg19: chr9-32541953;