9-32549604-T-C

Variant names:

• chr9-32549604-T-C
• rs628425
• NM_005802.5:c.198+1170A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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):

• inherited retinal dystrophy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 31

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288684 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOPORS	NM_005802.5	MANE Select	c.198+1170A>G		intron	N/A	NP_005793.2
	TOPORS	NM_001195622.2		c.3+2830A>G		intron	N/A	NP_001182551.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOPORS	ENST00000360538.7	TSL:1 MANE Select	c.198+1170A>G		intron	N/A	ENSP00000353735.2
	TOPORS	ENST00000379858.1	TSL:1	c.3+2830A>G		intron	N/A	ENSP00000369187.1
	ENSG00000288684	ENST00000681750.1		c.-45+1170A>G		intron	N/A	ENSP00000506413.1

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

African (AFR) AF: 0.417 AC: 17270 AN: 41434

American (AMR) AF: 0.206 AC: 3155 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3468

East Asian (EAS) AF: 0.00482 AC: 25 AN: 5188

South Asian (SAS) AF: 0.0976 AC: 471 AN: 4826

European-Finnish (FIN) AF: 0.217 AC: 2297 AN: 10578

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17064 AN: 67994

Other (OTH) AF: 0.255 AC: 538 AN: 2112

Alfa AF: 0.247 Hom.: 2821

Bravo AF: 0.278

Asia WGS AF: 0.0640 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.6
DANN	Benign	0.49
PhyloP100		0.43
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: rs628425; hg19: chr9-32549602; COSMIC: COSV62116512; COSMIC: COSV62116512;