NM_006493.4(CLN5):c.987T>G (p.Tyr329Ter) AND Neuronal ceroid lipofuscinosis

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 8, 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:: RCV001960560.5

Allele description

NM_006493.4(CLN5):c.987T>G (p.Tyr329Ter)

Gene:

CLN5:CLN5 intracellular trafficking protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q22.3

Genomic location:

Preferred name:

NM_006493.4(CLN5):c.987T>G (p.Tyr329Ter)

HGVS:

NC_000013.11:g.77000879T>G
NG_009064.1:g.13956T>G
NM_001366624.2:c.*436T>G
NM_006493.4:c.987T>GMANE SELECT
NP_006484.2:p.Tyr329Ter
LRG_692:g.13956T>G
NC_000013.10:g.77575014T>G

Protein change:

Y329*

Links:

dbSNP: rs2034349886

NCBI 1000 Genomes Browser:

rs2034349886

Molecular consequence:

NM_001366624.2:c.*436T>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_006493.4:c.987T>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Neuronal ceroid lipofuscinosis
Synonyms:: Ceroid storage disease
Identifiers:: MONDO: MONDO:0016295; MedGen: C0027877; Orphanet: 79263; OMIM: PS256730

Recent activity

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Homo sapiens ceramide kinase (CERK), mRNA
Homo sapiens ceramide kinase (CERK), mRNA
gi|1519241588|ref|NM_022766.6|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002227815	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 8, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9662406, 11971870, 20052765, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002227815

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 8, 2023)

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

CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis.

Savukoski M, Klockars T, Holmberg V, Santavuori P, Lander ES, Peltonen L.

Nat Genet. 1998 Jul;19(3):286-8.

PubMed [citation]

PMID:: 9662406

Lysosomal localization of the neuronal ceroid lipofuscinosis CLN5 protein.

Isosomppi J, Vesa J, Jalanko A, Peltonen L.

Hum Mol Genet. 2002 Apr 15;11(8):885-91.

PubMed [citation]

PMID:: 11971870

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002227815.3

#	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.Tyr378*) in the CLN5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 30 amino acid(s) of the CLN5 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CLN5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1454025). This variant disrupts a region of the CLN5 protein in which other variant(s) (p.Tyr392*) have been determined to be pathogenic (PMID: 9662406, 11971870, 20052765). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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: Mar 5, 2024

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