dbSNP rs146483990: TOPORS:p.Gly460Val (chr9-32543146-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005802.5(TOPORS):c.1379G>T(p.Gly460Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G460R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

TOPORS
NM_005802.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.282

Publications

1 publications found

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 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

TOPORS links:

ENSG00000288684 (HGNC:):

ENSG00000288684 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04542306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TOPORS	NM_005802.5 link	c.1379G>T	p.Gly460Val	missense_variant	Exon 3 of 3	ENST00000360538.7	NP_005793.2
TOPORS	NM_001195622.2 link	c.1184G>T	p.Gly395Val	missense_variant	Exon 2 of 2		NP_001182551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
TOPORS	ENST00000360538.7 link	c.1379G>T	p.Gly460Val	missense_variant	Exon 3 of 3	1	NM_005802.5	ENSP00000353735.2
TOPORS	ENST00000379858.1 link	c.1184G>T	p.Gly395Val	missense_variant	Exon 2 of 2	1		ENSP00000369187.1
ENSG00000288684	ENST00000681750.1 link	c.-45+7628G>T		intron_variant	Intron 3 of 19			ENSP00000506413.1
ENSG00000288684	ENST00000680198.1 link	n.198+7628G>T		intron_variant	Intron 2 of 18			ENSP00000505143.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.017

T;.

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.

PhyloP100

0.28

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.52

N;N

REVEL

Benign

0.034

Sift

Uncertain

0.012

D;D

Sift4G

Benign

0.067

T;T

Polyphen

0.097

B;.

Vest4

0.34

MVP

0.15

MPC

0.72

ClinPred

0.13

GERP RS

2.0

Varity_R

0.044

gMVP

0.21

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over