9-32541247-CAA-CA

Variant names:

• chr9-32541247-CA-C
• rs140010425
• NM_005802.5:c.*139delT

Variant summary

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

The NM_005802.5(TOPORS):​c.*139delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0256 in 757,988 control chromosomes in the GnomAD database, including 566 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (221 hom., cov: 29)
  • Exomes 𝑓: 0.024 (345 hom.)
• Consequence: TOPORS NM_005802.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.92
• Publications: 0 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, Labcorp Genetics (formerly Invitae)
• TOPORS-related retinopathy

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288684 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 9-32541247-CA-C is Benign according to our data. Variant chr9-32541247-CA-C is described in ClinVar as Likely_benign. ClinVar VariationId is 366554.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 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.*139delT		3_prime_UTR	Exon 3 of 3	NP_005793.2
	TOPORS	NM_001195622.2		c.*139delT		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.*139delT		3_prime_UTR	Exon 3 of 3	ENSP00000353735.2	Q9NS56-1
	TOPORS	ENST00000379858.1	TSL:1	c.*139delT		3_prime_UTR	Exon 2 of 2	ENSP00000369187.1	Q9NS56-2
	ENSG00000288684	ENST00000681750.1		c.-45+9526delT		intron	N/A	ENSP00000506413.1	A0A7P0TB70

Frequencies

GnomAD3 genomes AF: 0.0333 AC: 4947 AN: 148744 Hom.: 217 Cov.: 29

Gnomad AFR AF: 0.0916

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0178

Gnomad ASJ AF: 0.00638

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0388

Gnomad FIN AF: 0.000306

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.00221

Gnomad OTH AF: 0.0264

GnomAD4 exome AF: 0.0237 AC: 14443 AN: 609148 Hom.: 345 Cov.: 8 AF XY: 0.0243 AC XY: 7585 AN XY: 312390

African (AFR) AF: 0.110 AC: 1577 AN: 14376

American (AMR) AF: 0.0268 AC: 460 AN: 17178

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 195 AN: 14164

East Asian (EAS) AF: 0.157 AC: 4130 AN: 26304

South Asian (SAS) AF: 0.0535 AC: 2273 AN: 42496

European-Finnish (FIN) AF: 0.00786 AC: 210 AN: 26714

Middle Eastern (MID) AF: 0.0214 AC: 46 AN: 2148

European-Non Finnish (NFE) AF: 0.0106 AC: 4623 AN: 436288

Other (OTH) AF: 0.0315 AC: 929 AN: 29480

GnomAD4 genome AF: 0.0334 AC: 4964 AN: 148840 Hom.: 221 Cov.: 29 AF XY: 0.0342 AC XY: 2481 AN XY: 72474

African (AFR) AF: 0.0917 AC: 3723 AN: 40580

American (AMR) AF: 0.0177 AC: 264 AN: 14880

Ashkenazi Jewish (ASJ) AF: 0.00638 AC: 22 AN: 3450

East Asian (EAS) AF: 0.110 AC: 563 AN: 5102

South Asian (SAS) AF: 0.0388 AC: 182 AN: 4686

European-Finnish (FIN) AF: 0.000306 AC: 3 AN: 9794

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.00221 AC: 148 AN: 67090

Other (OTH) AF: 0.0266 AC: 55 AN: 2068

Alfa AF: 0.000132 Hom.: 63

ClinVar

ClinVar submissions as Germline

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		1.9
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: rs140010425; hg19: chr9-32541245; COSMIC: COSV62117717;