9-32542179-GGT-CGC

Variant names:

• chr9-32542179-GGT-CGC
• NM_005802.5:c.2344_2346delACCinsGCG
• TOPORS p.Thr782Ala

Variant summary

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

The NM_005802.5(TOPORS):​c.2344_2346delACCinsGCG​(p.Thr782Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. T782T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TOPORS NM_005802.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25
• Publications: 0 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, Labcorp Genetics (formerly Invitae), PanelApp Australia
• 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.2344_2346delACCinsGCG	p.Thr782Ala	missense	N/A	NP_005793.2
	TOPORS	NM_001195622.2		c.2149_2151delACCinsGCG	p.Thr717Ala	missense	N/A	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.2344_2346delACCinsGCG	p.Thr782Ala	missense	N/A	ENSP00000353735.2	Q9NS56-1
	TOPORS	ENST00000379858.1	TSL:1	c.2149_2151delACCinsGCG	p.Thr717Ala	missense	N/A	ENSP00000369187.1	Q9NS56-2
	ENSG00000288684	ENST00000681750.1		c.-45+8593_-45+8595delACCinsGCG		intron	N/A	ENSP00000506413.1	A0A7P0TB70

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-32542177;