Genetic Variant TOPORS:c.*137_*139dupTTT (chr9-32541247-C-CAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005802.5(TOPORS):c.*137_*139dupTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TOPORS
NM_005802.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.92

Publications

0 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):

retinitis pigmentosa 31
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
TOPORS-related retinopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
ciliopathy
Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

TOPORS links:

ENSG00000288684 (HGNC:):

ENSG00000288684 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOPORS	NM_005802.5	MANE Select	c.137_139dupTTT		3_prime_UTR	Exon 3 of 3	NP_005793.2
	TOPORS	NM_001195622.2		c.137_139dupTTT		3_prime_UTR	Exon 2 of 2	NP_001182551.1	Q9NS56-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TOPORS	ENST00000360538.7	TSL:1 MANE Select	c.137_139dupTTT	3_prime_UTR	Exon 3 of 3	ENSP00000353735.2	Q9NS56-1
TOPORS	ENST00000379858.1	TSL:1	c.137_139dupTTT	3_prime_UTR	Exon 2 of 2	ENSP00000369187.1	Q9NS56-2
ENSG00000288684	ENST00000681750.1		c.-45+9524_-45+9526dupTTT	intron	N/A	ENSP00000506413.1	A0A7P0TB70

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148802

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000317

AC:

AN:

631162

Hom.:

Cov.:

AF XY:

0.00000618

AC XY:

AN XY:

323764

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

14970

American (AMR)

AF:

0.00

AC:

AN:

18028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14694

East Asian (EAS)

AF:

0.00

AC:

AN:

27590

South Asian (SAS)

AF:

0.00

AC:

AN:

44630

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2236

European-Non Finnish (NFE)

AF:

0.00000222

AC:

AN:

450608

Other (OTH)

AF:

0.0000327

AC:

AN:

30590

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

148802

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72404

African (AFR)

AF:

0.00

AC:

AN:

40482

American (AMR)

AF:

0.00

AC:

AN:

14870

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5114

South Asian (SAS)

AF:

0.00

AC:

AN:

4696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67116

Other (OTH)

AF:

0.00

AC:

AN:

2046

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.9

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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9-32541247-CAA-CAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over