9-32550898-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000681750.1(ENSG00000288684):c.-169C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00986 in 1,612,974 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 7 hom., cov: 32)

Exomes 𝑓: 0.010 ( 100 hom. )

Consequence

ENSG00000288684
ENST00000681750.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.417

Variant links:

Genes affected

ENSG00000288684 (HGNC:):

ENSG00000288684 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037550926).

BP6

Variant 9-32550898-G-C is Benign according to our data. Variant chr9-32550898-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 195250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-32550898-G-C is described in Lovd as [Likely_pathogenic].

BS2

High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOPORS	NM_005802.5 link	c.74C>G	p.Ser25Trp	missense_variant	Exon 2 of 3	ENST00000360538.7	NP_005793.2	Q9NS56-1
TOPORS	NM_001195622.2 link	c.3+1536C>G		intron_variant	Intron 1 of 1		NP_001182551.1	Q9NS56-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENSG00000288684	ENST00000681750.1 link	c.-169C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 20			ENSP00000506413.1	A0A7P0TB70
TOPORS	ENST00000360538.7 link	c.74C>G	p.Ser25Trp	missense_variant	Exon 2 of 3	1	NM_005802.5	ENSP00000353735.2	Q9NS56-1
ENSG00000288684	ENST00000681750.1 link	c.-169C>G		5_prime_UTR_variant	Exon 3 of 20			ENSP00000506413.1	A0A7P0TB70

Frequencies

GnomAD3 genomes

AF:

0.00694

AC:

1057

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0203

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0102

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00825

AC:

2001

AN:

242688

Hom.:

AF XY:

0.00817

AC XY:

1084

AN XY:

132680

show subpopulations

Gnomad AFR exome

AF:

0.00180

Gnomad AMR exome

AF:

0.00643

Gnomad ASJ exome

AF:

0.00143

Gnomad EAS exome

AF:

0.000612

Gnomad SAS exome

AF:

0.00174

Gnomad FIN exome

AF:

0.0230

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.00685

GnomAD4 exome

AF:

0.0102

AC:

14853

AN:

1460640

Hom.:

100

Cov.:

AF XY:

0.0100

AC XY:

7269

AN XY:

726682

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.00582

Gnomad4 ASJ exome

AF:

0.00153

Gnomad4 EAS exome

AF:

0.000529

Gnomad4 SAS exome

AF:

0.00186

Gnomad4 FIN exome

AF:

0.0220

Gnomad4 NFE exome

AF:

0.0114

Gnomad4 OTH exome

AF:

0.00817

GnomAD4 genome

AF:

0.00693

AC:

1056

AN:

152334

Hom.:

Cov.:

AF XY:

0.00713

AC XY:

531

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0203

Gnomad4 NFE

AF:

0.0102

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00390

Hom.:

Bravo

AF:

0.00596

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00923

AC:

ExAC

AF:

0.00811

AC:

982

EpiCase

AF:

0.00911

EpiControl

AF:

0.0101

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 24, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ENSG00000288684: BS1, BS2; TOPORS: BS1, BS2 -

not specified

Benign:1

Aug 25, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 31

Benign:1

Sep 24, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Retinitis pigmentosa

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0078

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.23

REVEL

Benign

0.067

Sift

Uncertain

0.020

Sift4G

Uncertain

0.021

Polyphen

0.69

Vest4

0.33

MVP

0.19

MPC

0.73

ClinPred

0.020

GERP RS

3.4

Varity_R

0.073

gMVP

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over