rs34721491

Variant names:

• chr9-32541024-CAA-C
• rs34721491
• NM_005802.5:c.*361_*362delTT

Your query was ambiguous. Multiple possible variants found:

• chr9-32541024-CAA-C
• chr9-32541024-CAA-CA
• chr9-32541024-CAA-CAAA
• chr9-32541024-CAA-CAAAA
• chr9-32541024-CAA-CAAAAA

Variant summary

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

The NM_005802.5(TOPORS):​c.*361_*362delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 164,610 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 20)
  • Exomes 𝑓: 0.00095 (0 hom.)
• Consequence: TOPORS NM_005802.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 1 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):

• 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

ENSG00000288684 (HGNC:):

ACMG classification

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.*361_*362delTT		3_prime_UTR	Exon 3 of 3	NP_005793.2
	TOPORS	NM_001195622.2		c.*361_*362delTT		3_prime_UTR	Exon 2 of 2	NP_001182551.1	Q9NS56-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOPORS	ENST00000360538.7	TSL:1 MANE Select	c.*361_*362delTT		3_prime_UTR	Exon 3 of 3	ENSP00000353735.2	Q9NS56-1
	TOPORS	ENST00000379858.1	TSL:1	c.*361_*362delTT		3_prime_UTR	Exon 2 of 2	ENSP00000369187.1	Q9NS56-2
	ENSG00000288684	ENST00000681750.1		c.-45+9748_-45+9749delTT		intron	N/A	ENSP00000506413.1	A0A7P0TB70

Frequencies

GnomAD3 genomes AF: 0.00000686 AC: 1 AN: 145674 Hom.: 0 Cov.: 20

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: 0.000110

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000951 AC: 18 AN: 18936 Hom.: 0 AF XY: 0.000978 AC XY: 10 AN XY: 10228

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

African (AFR) AF: 0.00 AC: 0 AN: 196

American (AMR) AF: 0.00 AC: 0 AN: 2134

Ashkenazi Jewish (ASJ) AF: 0.00357 AC: 1 AN: 280

East Asian (EAS) AF: 0.00 AC: 0 AN: 986

South Asian (SAS) AF: 0.000701 AC: 2 AN: 2854

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 24

European-Non Finnish (NFE) AF: 0.00141 AC: 15 AN: 10672

Other (OTH) AF: 0.00 AC: 0 AN: 760

⚠️ 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.

GnomAD4 genome AF: 0.00000686 AC: 1 AN: 145674 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 70624

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

African (AFR) AF: 0.00 AC: 0 AN: 39280

American (AMR) AF: 0.00 AC: 0 AN: 14576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3412

East Asian (EAS) AF: 0.00 AC: 0 AN: 4942

South Asian (SAS) AF: 0.00 AC: 0 AN: 4666

European-Finnish (FIN) AF: 0.000110 AC: 1 AN: 9072

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66518

Other (OTH) AF: 0.00 AC: 0 AN: 2012

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 138

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8

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: rs34721491; hg19: chr9-32541022;