NM_004937.3(CTNS):c.18_21del (p.Thr7fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 18, 2024
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:: RCV002516530.9

Allele description [Variation Report for NM_004937.3(CTNS):c.18_21del (p.Thr7fs)]

NM_004937.3(CTNS):c.18_21del (p.Thr7fs)

Gene:

CTNS:cystinosin, lysosomal cystine transporter [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17p13.2

Genomic location:

Preferred name:

NM_004937.3(CTNS):c.18_21del (p.Thr7fs)

HGVS:

NC_000017.10:g.3543516_3543519del
NC_000017.11:g.3640224_3640227del
NG_012489.2:g.8757_8760del
NG_052852.1:g.1098_1101del
NM_001031681.3:c.18_21del
NM_001374492.1:c.18_21del
NM_001374493.1:c.-339_-336del
NM_001374494.1:c.-381+2908_-381+2911del
NM_001374495.1:c.-260_-257del
NM_001374496.1:c.-296+2908_-296+2911del
NM_004937.3:c.18_21delMANE SELECT
NP_001026851.2:p.Thr7fs
NP_001361421.1:p.Thr7fs
NP_004928.2:p.Thr7fs
NC_000017.10:g.3543516_3543519del
NC_000017.10:g.3543518_3543521del
NC_000017.10:g.3543518_3543521delGACT
NM_001031681.2:c.18_21delGACT
NM_001031681.3:c.18_21del
NM_004937.2:c.18_21delGACT
NM_004937.3:c.18_21delGACTMANE SELECT
NP_004928.2:p.Thr7PhefsTer7

Protein change:

T7fs

Links:

OMIM: 606272.0004; dbSNP: rs786204501

NCBI 1000 Genomes Browser:

rs786204501

Molecular consequence:

NM_001374493.1:c.-339_-336del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001374495.1:c.-260_-257del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001031681.3:c.18_21del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374492.1:c.18_21del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004937.3:c.18_21del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374494.1:c.-381+2908_-381+2911del - intron variant - [Sequence Ontology: SO:0001627]
NM_001374496.1:c.-296+2908_-296+2911del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Ocular cystinosis
Synonyms:: Cystinosis, ocular nonnephropathic; Cystinosis, adult, nonnephropathic; Cystinosis, benign, nonnephropathic
Identifiers:: MONDO: MONDO:0009064; MedGen: C2931013; Orphanet: 213; OMIM: 219750

Name:: Juvenile nephropathic cystinosis
Synonyms:: CYSTINOSIS, LATE-ONSET JUVENILE OR ADOLESCENT NEPHROPATHIC TYPE
Identifiers:: MONDO: MONDO:0009066; MedGen: C0268626; Orphanet: 213; Orphanet: 411634; OMIM: 219900

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000827371	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 18, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27102039, 9537412, 28276207, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000827371

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 18, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Cystinosis: a review.

Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E.

Orphanet J Rare Dis. 2016 Apr 22;11:47. doi: 10.1186/s13023-016-0426-y. Review.

PubMed [citation]

PMID:: 27102039
PMCID:: PMC4841061

A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis.

Town M, Jean G, Cherqui S, Attard M, Forestier L, Whitmore SA, Callen DF, Gribouval O, Broyer M, Bates GP, van't Hoff W, Antignac C.

Nat Genet. 1998 Apr;18(4):319-24.

PubMed [citation]

PMID:: 9537412

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000827371.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Thr7Phefs*7) in the CTNS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CTNS are known to be pathogenic (PMID: 9537412, 27102039). This variant is present in population databases (rs764835663, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with nephropathic cystinosis (PMID: 9537412, 28276207). ClinVar contains an entry for this variant (Variation ID: 188834). For these reasons, this variant has been classified as Pathogenic.

#	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: May 12, 2024

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Relating variation to medicine