9-32541024-CA-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005802.5(TOPORS):​c.*362delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1016 hom., cov: 20)
  • Exomes 𝑓: 0.15 (43 hom.)
• Consequence: TOPORS NM_005802.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 9-32541024-CA-C is Benign according to our data. Variant chr9-32541024-CA-C is described in ClinVar as Likely_benign. ClinVar VariationId is 366551.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 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.*362delT		3_prime_UTR	Exon 3 of 3	NP_005793.2
	TOPORS	NM_001195622.2		c.*362delT		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.*362delT		3_prime_UTR	Exon 3 of 3	ENSP00000353735.2	Q9NS56-1
	TOPORS	ENST00000379858.1	TSL:1	c.*362delT		3_prime_UTR	Exon 2 of 2	ENSP00000369187.1	Q9NS56-2
	ENSG00000288684	ENST00000681750.1		c.-45+9749delT		intron	N/A	ENSP00000506413.1	A0A7P0TB70

Frequencies

GnomAD3 genomes AF: 0.108 AC: 15713 AN: 145572 Hom.: 1016 Cov.: 20

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.0920

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.147 AC: 2681 AN: 18238 Hom.: 43 Cov.: 0 AF XY: 0.149 AC XY: 1459 AN XY: 9822

African (AFR) AF: 0.0860 AC: 16 AN: 186

American (AMR) AF: 0.135 AC: 274 AN: 2028

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 50 AN: 276

East Asian (EAS) AF: 0.0851 AC: 79 AN: 928

South Asian (SAS) AF: 0.110 AC: 299 AN: 2714

European-Finnish (FIN) AF: 0.176 AC: 179 AN: 1018

Middle Eastern (MID) AF: 0.208 AC: 5 AN: 24

European-Non Finnish (NFE) AF: 0.160 AC: 1650 AN: 10330

Other (OTH) AF: 0.176 AC: 129 AN: 734

GnomAD4 genome AF: 0.108 AC: 15716 AN: 145646 Hom.: 1016 Cov.: 20 AF XY: 0.106 AC XY: 7508 AN XY: 70656

African (AFR) AF: 0.0354 AC: 1395 AN: 39356

American (AMR) AF: 0.0918 AC: 1339 AN: 14584

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 712 AN: 3412

East Asian (EAS) AF: 0.0152 AC: 75 AN: 4928

South Asian (SAS) AF: 0.0692 AC: 322 AN: 4654

European-Finnish (FIN) AF: 0.153 AC: 1386 AN: 9046

Middle Eastern (MID) AF: 0.295 AC: 82 AN: 278

European-Non Finnish (NFE) AF: 0.150 AC: 9984 AN: 66468

Other (OTH) AF: 0.128 AC: 259 AN: 2028

Alfa AF: 0.0607 Hom.: 138

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Retinitis Pigmentosa, Dominant (1)

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: COSV62117799;