Variant 9-32543146-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005802.5(TOPORS):c.1379G>C(p.Gly460Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TOPORS
NM_005802.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 0.282

Variant links:

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 links:

ENSG00000288684 (HGNC:):

ENSG00000288684 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032795727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOPORS	NM_005802.5 linkuse as main transcript	c.1379G>C	p.Gly460Ala	missense_variant	3/3	ENST00000360538.7	NP_005793.2	Q9NS56-1
TOPORS	NM_001195622.2 linkuse as main transcript	c.1184G>C	p.Gly395Ala	missense_variant	2/2		NP_001182551.1	Q9NS56-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TOPORS	ENST00000360538.7 linkuse as main transcript	c.1379G>C	p.Gly460Ala	missense_variant	3/3	1	NM_005802.5	ENSP00000353735.2	Q9NS56-1
TOPORS	ENST00000379858.1 linkuse as main transcript	c.1184G>C	p.Gly395Ala	missense_variant	2/2	1		ENSP00000369187.1	Q9NS56-2
ENSG00000288684	ENST00000681750.1 linkuse as main transcript	c.-45+7628G>C		intron_variant				ENSP00000506413.1	A0A7P0TB70
ENSG00000288684	ENST00000680198.1 linkuse as main transcript	c.198+7628G>C		intron_variant				ENSP00000505143.1	A0A7P0T8K8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461756

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Retinitis pigmentosa 31

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Jan 01, 2016

This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PM2. -

Macular degeneration;C0344232:Blurred vision;C1862475:Abnormality of retinal pigmentation;C4551715:Pigmentary retinopathy

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Jan 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

9.8

DANN

Benign

0.68

DEOGEN2

Benign

0.015

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.53

N;N

REVEL

Benign

0.020

Sift

Benign

0.031

D;D

Sift4G

Benign

0.19

T;T

Polyphen

0.0

B;.

Vest4

0.10

MutPred

0.30

Loss of sheet (P = 7e-04);.;

MVP

0.12

MPC

0.35

ClinPred

0.099

GERP RS

2.0

Varity_R

0.037

gMVP

0.18

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