chr9-32541389-A-T

Position:

• chr9-32541389-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_005802.5(TOPORS):​c.3136T>A​(p.Ter1046LysextTer13) variant causes a stop lost 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TOPORS NM_005802.5 stop_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.87

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_005802.5 Downstream stopcodon found after 979 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TOPORS	NM_005802.5	c.3136T>A	p.Ter1046LysextTer13	stop_lost	3/3	ENST00000360538.7	NP_005793.2
TOPORS	NM_001195622.2	c.2941T>A	p.Ter981LysextTer13	stop_lost	2/2		NP_001182551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TOPORS	ENST00000360538.7	c.3136T>A	p.Ter1046LysextTer13	stop_lost	3/3	1	NM_005802.5	ENSP00000353735	P3
TOPORS	ENST00000379858.1	c.2941T>A	p.Ter981LysextTer13	stop_lost	2/2	1		ENSP00000369187	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 05, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 1449765). This variant has not been reported in the literature in individuals affected with TOPORS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change disrupts the translational stop signal of the TOPORS mRNA. It is expected to extend the length of the TOPORS protein by 13 additional amino acid residues. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.43
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.93	D
MutationTaster	Benign	1.0	N;N
Vest4		0.33
GERP RS		2.9

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-32541387;