rs628425

chr9-32549604-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005802.5(TOPORS):c.198+1170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,098 control chromosomes in the GnomAD database, including 6,499 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (6499 hom., cov: 32)
• Consequence: TOPORS NM_005802.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOPORS	NM_005802.5	c.198+1170A>G		intron_variant		ENST00000360538.7
TOPORS	NM_001195622.2	c.3+2830A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOPORS	ENST00000360538.7	c.198+1170A>G		intron_variant		1	NM_005802.5	P3
TOPORS	ENST00000379858.1	c.3+2830A>G		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41625 AN: 151982 Hom.: 6490 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.0973

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.259

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.274 AC: 41648 AN: 152098 Hom.: 6499 Cov.: 32 AF XY: 0.267 AC XY: 19866 AN XY: 74364

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.00482

Gnomad4 SAS AF: 0.0976

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.255

Alfa AF: 0.246 Hom.: 2531

Bravo AF: 0.278

Asia WGS AF: 0.0640 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.6
Dann	Benign	0.49

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: rs628425; hg19: chr9-32549602; COSMIC: COSV62116512; COSMIC: COSV62116512;