NM_005802.5(TOPORS):c.3126_3127del (p.Cys1042_Asp1043delinsTer) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 9, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001210346.6

Allele description [Variation Report for NM_005802.5(TOPORS):c.3126_3127del (p.Cys1042_Asp1043delinsTer)]

NM_005802.5(TOPORS):c.3126_3127del (p.Cys1042_Asp1043delinsTer)

Gene:

TOPORS:TOP1 binding arginine/serine rich protein, E3 ubiquitin ligase [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

9p21.1

Genomic location:

Preferred name:

NM_005802.5(TOPORS):c.3126_3127del (p.Cys1042_Asp1043delinsTer)

HGVS:

NC_000009.12:g.32541398CA[1]
NG_017050.1:g.16224TG[1]
NM_001195622.2:c.2931_2932del
NM_005802.5:c.3126_3127delMANE SELECT
NP_001182551.1:p.Cys977_Asp978delinsTer
NP_005793.2:p.Cys1042_Asp1043delinsTer
NC_000009.11:g.32541396CA[1]
NC_000009.11:g.32541396_32541397del
NM_005802.4:c.3126_3127del

Links:

dbSNP: rs776001696

NCBI 1000 Genomes Browser:

rs776001696

Molecular consequence:

NM_001195622.2:c.2931_2932del - nonsense - [Sequence Ontology: SO:0001587]
NM_005802.5:c.3126_3127del - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001381829	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jun 9, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001381829

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jun 9, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001381829.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. ClinVar contains an entry for this variant (Variation ID: 940703). This premature translational stop signal has been observed in individuals with clinical features of retinitis pigmentosa (Invitae). This variant is present in population databases (rs776001696, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Cys1042*) in the TOPORS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 4 amino acid(s) of the TOPORS protein.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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