chr9-32541247-CA-C

Position:

• chr9-32541247-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005802.5(TOPORS):​c.*139del 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

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 Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOPORS	NM_005802.5	c.*139del		3_prime_UTR_variant	3/3	ENST00000360538.7	NP_005793.2
TOPORS	NM_001195622.2	c.*139del		3_prime_UTR_variant	2/2		NP_001182551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOPORS	ENST00000360538.7	c.*139del		3_prime_UTR_variant	3/3	1	NM_005802.5	ENSP00000353735	P3
TOPORS	ENST00000379858.1	c.*139del		3_prime_UTR_variant	2/2	1		ENSP00000369187	A1

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

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.0268

Gnomad4 ASJ exome AF: 0.0138

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.0535

Gnomad4 FIN exome AF: 0.00786

Gnomad4 NFE exome AF: 0.0106

Gnomad4 OTH exome AF: 0.0315

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

Gnomad4 AFR AF: 0.0917

Gnomad4 AMR AF: 0.0177

Gnomad4 ASJ AF: 0.00638

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.0388

Gnomad4 FIN AF: 0.000306

Gnomad4 NFE AF: 0.00221

Gnomad4 OTH AF: 0.0266

Alfa AF: 0.000132 Hom.: 63

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis Pigmentosa, Dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs140010425; hg19: chr9-32541245;