9-32541024-CAA-CAAA

Variant names:

• chr9-32541024-C-CA
• rs34721491
• NM_005802.5:c.*362dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_005802.5(TOPORS):​c.*362dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2758 hom., cov: 20)
  • Exomes 𝑓: 0.21 (64 hom.)
• Consequence: TOPORS NM_005802.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606
• Publications: 1 publications found

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]

TOPORS Gene-Disease associations (from GenCC):

• retinitis pigmentosa 31

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• TOPORS-related retinopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ciliopathy

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ENSG00000288684 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005802.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOPORS	NM_005802.5	MANE Select	c.*362dupT		3_prime_UTR	Exon 3 of 3	NP_005793.2
	TOPORS	NM_001195622.2		c.*362dupT		3_prime_UTR	Exon 2 of 2	NP_001182551.1	Q9NS56-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOPORS	ENST00000360538.7	TSL:1 MANE Select	c.*362dupT		3_prime_UTR	Exon 3 of 3	ENSP00000353735.2	Q9NS56-1
	TOPORS	ENST00000379858.1	TSL:1	c.*362dupT		3_prime_UTR	Exon 2 of 2	ENSP00000369187.1	Q9NS56-2
	ENSG00000288684	ENST00000681750.1		c.-45+9749dupT		intron	N/A	ENSP00000506413.1	A0A7P0TB70

Frequencies

GnomAD3 genomes AF: 0.181 AC: 26294 AN: 145520 Hom.: 2762 Cov.: 20

Gnomad AFR AF: 0.0801

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.00648

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.200

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.198

GnomAD4 exome AF: 0.207 AC: 3821 AN: 18426 Hom.: 64 Cov.: 0 AF XY: 0.201 AC XY: 2003 AN XY: 9948

African (AFR) AF: 0.0885 AC: 17 AN: 192

American (AMR) AF: 0.207 AC: 418 AN: 2020

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 55 AN: 276

East Asian (EAS) AF: 0.0832 AC: 79 AN: 950

South Asian (SAS) AF: 0.172 AC: 474 AN: 2756

European-Finnish (FIN) AF: 0.197 AC: 201 AN: 1018

Middle Eastern (MID) AF: 0.0455 AC: 1 AN: 22

European-Non Finnish (NFE) AF: 0.233 AC: 2437 AN: 10452

Other (OTH) AF: 0.188 AC: 139 AN: 740

GnomAD4 genome AF: 0.181 AC: 26291 AN: 145598 Hom.: 2758 Cov.: 20 AF XY: 0.179 AC XY: 12632 AN XY: 70620

African (AFR) AF: 0.0801 AC: 3150 AN: 39346

American (AMR) AF: 0.168 AC: 2447 AN: 14574

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 592 AN: 3406

East Asian (EAS) AF: 0.00649 AC: 32 AN: 4930

South Asian (SAS) AF: 0.114 AC: 531 AN: 4654

European-Finnish (FIN) AF: 0.232 AC: 2095 AN: 9042

Middle Eastern (MID) AF: 0.198 AC: 55 AN: 278

European-Non Finnish (NFE) AF: 0.253 AC: 16830 AN: 66444

Other (OTH) AF: 0.195 AC: 395 AN: 2030

Alfa AF: 0.104 Hom.: 138

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34721491; hg19: chr9-32541022; COSMIC: COSV62115991;