9-32541247-C-CA

Position:

• chr9-32541247-C-CA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005802.5(TOPORS):​c.*139_*140insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 768,070 control chromosomes in the GnomAD database, including 3,004 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1232 hom., cov: 29)
  • Exomes 𝑓: 0.14 (1772 hom.)
• Consequence: TOPORS NM_005802.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U: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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOPORS	NM_005802.5	c.*139_*140insT		3_prime_UTR_variant	3/3	ENST00000360538.7	NP_005793.2
TOPORS	NM_001195622.2	c.*139_*140insT		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.*139_*140insT		3_prime_UTR_variant	3/3	1	NM_005802.5	ENSP00000353735	P3
TOPORS	ENST00000379858.1	c.*139_*140insT		3_prime_UTR_variant	2/2	1		ENSP00000369187	A1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 17637 AN: 148754 Hom.: 1232 Cov.: 29

Gnomad AFR AF: 0.0536

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.0993

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0154

Gnomad SAS AF: 0.0722

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.139 AC: 86350 AN: 619220 Hom.: 1772 Cov.: 8 AF XY: 0.139 AC XY: 44056 AN XY: 317618

Gnomad4 AFR exome AF: 0.0596

Gnomad4 AMR exome AF: 0.0920

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.0172

Gnomad4 SAS exome AF: 0.0824

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.119 AC: 17646 AN: 148850 Hom.: 1232 Cov.: 29 AF XY: 0.116 AC XY: 8418 AN XY: 72486

Gnomad4 AFR AF: 0.0538

Gnomad4 AMR AF: 0.0991

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.0153

Gnomad4 SAS AF: 0.0721

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.143

Bravo AF: 0.112

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis Pigmentosa, Dominant Uncertain:1

Uncertain significance, 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;