ClinVar Genomic variation as it relates to human health
NM_001042432.2(CLN3):c.883G>T (p.Glu295Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001042432.2(CLN3):c.883G>T (p.Glu295Ter)
Variation ID: 56290 Accession: VCV000056290.13
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 16p12.1 16: 28482500 (GRCh38) [ NCBI UCSC ] 16: 28493821 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jul 24, 2013 Feb 14, 2024 Jan 11, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001042432.2:c.883G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001035897.1:p.Glu295Ter nonsense NM_000086.2:c.883G>T NP_000077.1:p.Glu295Ter nonsense NM_001286104.2:c.811G>T NP_001273033.1:p.Glu271Ter nonsense NM_001286105.2:c.583G>T NP_001273034.1:p.Glu195Ter nonsense NM_001286109.2:c.649G>T NP_001273038.1:p.Glu217Ter nonsense NM_001286110.2:c.721G>T NP_001273039.1:p.Glu241Ter nonsense NC_000016.10:g.28482500C>A NC_000016.9:g.28493821C>A NG_008654.2:g.14803G>T LRG_689:g.14803G>T LRG_689t1:c.883G>T LRG_689p1:p.Glu295Ter LRG_689t2:c.883G>T LRG_689p2:p.Glu295Ter - Protein change
- E295*, E241*, E271*, E195*, E217*
- Other names
- -
- Canonical SPDI
- NC_000016.10:28482499:C:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.00020 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
CLN3 | - | - |
GRCh38 GRCh37 |
1118 | 1201 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Oct 20, 2023 | RCV000049702.4 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jan 11, 2024 | RCV001055217.7 | |
Pathogenic (1) |
criteria provided, single submitter
|
Oct 8, 2020 | RCV001552759.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Pathogenic
(Jan 11, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Neuronal ceroid lipofuscinosis
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001219595.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Glu295*) in the CLN3 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Glu295*) in the CLN3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CLN3 are known to be pathogenic (PMID: 9311735, 28542676). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with retinal degeneration (PMID: 28542676). ClinVar contains an entry for this variant (Variation ID: 56290). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Likely pathogenic
(Jul 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Neuronal ceroid lipofuscinosis 3
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000793104.1
First in ClinVar: Jul 24, 2013 Last updated: Jul 24, 2013 |
|
|
Pathogenic
(Mar 11, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Neuronal ceroid lipofuscinosis
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001519540.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
Variant summary: CLN3 c.883G>T (p.Glu295X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: CLN3 c.883G>T (p.Glu295X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251470 control chromosomes (gnomAD). c.883G>T has been reported in the literature in individuals affected with Juvenile Neuronal Ceroid-Lipofuscinosis (Juvenile Batten Disease) and isolated retinal degeneration (Zhong_2000, Kousi_2012, Bell_2011, Ku_2017, Turriff_2019). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
Pathogenic
(Oct 08, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001773508.1
First in ClinVar: Aug 07, 2021 Last updated: Aug 07, 2021 |
Comment:
Identified in a patient with suspected JNCL who did not have a second identifiable CLN3 variant (Kousi et al., 2012); Nonsense variant predicted to result … (more)
Identified in a patient with suspected JNCL who did not have a second identifiable CLN3 variant (Kousi et al., 2012); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 21990111, 31741823, 28542676, 31568712, 30769084, 11339651, 25525159, 21228398) (less)
|
|
Pathogenic
(Aug 10, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Neuronal ceroid lipofuscinosis 3
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV001977443.1
First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
|
|
Pathogenic
(Oct 20, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Neuronal ceroid lipofuscinosis 3
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004214306.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
probable-pathogenic
(-)
|
no assertion criteria provided
Method: not provided
|
Juvenile neuronal ceroid lipofuscinosis
Affected status: not provided
Allele origin:
not provided
|
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)
Accession: SCV000082109.1
First in ClinVar: Jul 24, 2013 Last updated: Jul 24, 2013
Comment:
FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference
|
Comment:
Converted during submission to Likely pathogenic.
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Novel homozygous CLN3 missense variant in isolated retinal dystrophy: A case report and electron microscopic findings. | Mizobuchi K | Molecular genetics & genomic medicine | 2020 | PMID: 32441891 |
Considerations in multi-gene panel testing in pediatric ophthalmology. | Turriff AE | Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus | 2019 | PMID: 30769084 |
Detailed Clinical Phenotype and Molecular Genetic Findings in CLN3-Associated Isolated Retinal Degeneration. | Ku CA | JAMA ophthalmology | 2017 | PMID: 28542676 |
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. | Xiong HY | Science (New York, N.Y.) | 2015 | PMID: 25525159 |
Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. | Kousi M | Human mutation | 2012 | PMID: 21990111 |
Carrier testing for severe childhood recessive diseases by next-generation sequencing. | Bell CJ | Science translational medicine | 2011 | PMID: 21228398 |
Heterogeneity of late-infantile neuronal ceroid lipofuscinosis. | Zhong N | Genetics in medicine : official journal of the American College of Medical Genetics | 2000 | PMID: 11339651 |
Spectrum of mutations in the Batten disease gene, CLN3. | Munroe PB | American journal of human genetics | 1997 | PMID: 9311735 |
Text-mined citations for rs121434286 ...
HelpRecord last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.