ClinVar Genomic variation as it relates to human health
NC_000015.9:g.68504037_68504039delGAT
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
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NM_017882.2(CLN6):c.461_463del (p.Ile154del)
Variation ID: 4083 Accession: VCV000004083.40
- Type and length
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Microsatellite, 3 bp
- Location
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Cytogenetic: 15q23 15: 68211698-68211700 (GRCh38) [ NCBI UCSC ] 15: 68504036-68504038 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Oct 1, 2013 Aug 4, 2024 Dec 18, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_017882.3:c.458TCA[1] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_060352.1:p.Ile154del inframe deletion NM_017882.3:c.461_463del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_017882.2:c.461_463del NC_000015.10:g.68211700ATG[1] NC_000015.9:g.68504038ATG[1] NG_008764.2:g.50509TCA[1] LRG_832:g.50509TCA[1] LRG_832t1:c.458TCA[1] LRG_832p1:p.Ile154del - Protein change
- I154del
- Other names
- I154delI
- Canonical SPDI
- NC_000015.10:68211697:TGATGATG:TGATG
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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
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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. |
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CLN6 | - | - |
GRCh38 GRCh37 |
765 | 781 |
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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Feb 11, 2022 | RCV000004298.12 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Dec 18, 2023 | RCV000989354.8 | |
See cases
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Likely pathogenic (1) |
criteria provided, single submitter
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Dec 26, 2019 | RCV002251873.3 |
Likely pathogenic (1) |
criteria provided, single submitter
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Aug 23, 2021 | RCV002490306.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 1, 2017 | RCV001091349.20 |
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
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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
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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. |
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Likely pathogenic
(Dec 26, 2019)
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criteria provided, single submitter
Method: clinical testing
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See cases
Affected status: yes
Allele origin:
germline
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Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Accession: SCV002523398.1
First in ClinVar: Jun 09, 2022 Last updated: Jun 09, 2022 |
Comment:
ACMG classification criteria: PS4, PM2, PM3, PM4, PP3
Clinical Features:
Seizure (present) , Neurodevelopmental abnormality (present) , Loss of speech (present) , Gait disturbance (present) , Dysphagia (present)
Geographic origin: Brazil
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Pathogenic
(Feb 11, 2022)
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criteria provided, single submitter
Method: clinical testing
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Ceroid lipofuscinosis, neuronal, 6A
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002581425.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PS4, PM3, PM4, PS3_SUP, PM2_SUP, PP1
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Number of individuals with the variant: 1
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Likely pathogenic
(Aug 23, 2021)
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criteria provided, single submitter
Method: clinical testing
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Ceroid lipofuscinosis, neuronal, 6B (Kufs type)
Ceroid lipofuscinosis, neuronal, 6A
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002795717.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Dec 18, 2023)
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criteria provided, single submitter
Method: clinical testing
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Neuronal ceroid lipofuscinosis
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001207577.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This variant, c.461_463del, results in the deletion of 1 amino acid(s) of the CLN6 protein (p.Ile154del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.461_463del, results in the deletion of 1 amino acid(s) of the CLN6 protein (p.Ile154del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs121908080, gnomAD 0.003%). This variant has been observed in individuals with CLN6-related conditions (PMID: 11727201, 12673792, 21990111). ClinVar contains an entry for this variant (Variation ID: 4083). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects CLN6 function (PMID: 20020536). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Mar 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001247326.24
First in ClinVar: May 12, 2020 Last updated: Aug 04, 2024 |
Number of individuals with the variant: 1
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Likely pathogenic
(Sep 18, 2017)
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criteria provided, single submitter
Method: clinical testing
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Ceroid lipofuscinosis, neuronal, 6A
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000794168.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Pathogenic
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Neuronal ceroid lipofuscinosis 1
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001139645.1
First in ClinVar: Jan 11, 2020 Last updated: Jan 11, 2020 |
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Pathogenic
(Feb 20, 2023)
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criteria provided, single submitter
Method: clinical testing
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Neuronal ceroid lipofuscinosis
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003845049.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
Comment:
Variant summary: CLN6 c.461_463delTCA (p.Ile154del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele … (more)
Variant summary: CLN6 c.461_463delTCA (p.Ile154del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 4e-06 in 251134 control chromosomes (gnomAD). c.461_463delTCA has been reported in the literature in several homozygous and compound heterozygous individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) (e.g. Teixeira_2003, Bouhouche_2012). These data indicate that the variant is very likely to be associated with disease. At least one publication reported experimental evidence evaluating an impact on protein function, and demonstrated decreased half-life for the variant protein (Kurze_2010). Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and all laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(May 01, 2003)
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no assertion criteria provided
Method: literature only
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CEROID LIPOFUSCINOSIS, NEURONAL, 6A
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000024464.4
First in ClinVar: Apr 04, 2013 Last updated: Dec 04, 2021 |
Comment on evidence:
In a family from Portugal, Wheeler et al. (2002) found that variant late infantile neuronal ceroid lipofuscinosis (CLN6A; 601780) was caused by a 3-bp deletion … (more)
In a family from Portugal, Wheeler et al. (2002) found that variant late infantile neuronal ceroid lipofuscinosis (CLN6A; 601780) was caused by a 3-bp deletion (460_462delATC) in exon 4 of the CLN6 gene, resulting in the loss of the ile154 codon (I154del). Teixeira et al. (2003) concluded that the I154del mutation accounts for 81.25% of mutated CLN6 alleles in Portuguese patients with CLN6A. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: research
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Ceroid lipofuscinosis, neuronal, 6A
Affected status: yes
Allele origin:
inherited
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Translational Research Program on Neuronal Ceroid Lipofuscinosis, Center for the Study of Inborn Errors of Metabolism
Accession: SCV000804305.1
First in ClinVar: Aug 12, 2018 Last updated: Aug 12, 2018 |
Comment:
Late Infantile NCL
Number of individuals with the variant: 1
Age: 10-19 years
Sex: female
Geographic origin: Argentina
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not provided
(-)
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no classification provided
Method: literature only
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Ceroid lipofuscinosis, neuronal, 6A
Affected status: not provided
Allele origin:
unknown
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GeneReviews
Accession: SCV000086974.2
First in ClinVar: Oct 01, 2013 Last updated: Oct 01, 2022 |
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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 |
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CLN6 p.I154del mutation causing late infantile neuronal ceroid lipofuscinosis in a large consanguineous Moroccan family. | Bouhouche A | Indian journal of pediatrics | 2013 | PMID: 23180398 |
Neuronal Ceroid-Lipofuscinoses – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. | Adam MP | - | 2013 | PMID: 20301601 |
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 |
Pathogenic mutations cause rapid degradation of lysosomal storage disease-related membrane protein CLN6. | Kurze AK | Human mutation | 2010 | PMID: 20020536 |
CLN6, which is associated with a lysosomal storage disease, is an endoplasmic reticulum protein. | Mole SE | Experimental cell research | 2004 | PMID: 15265688 |
Novel mutations in the CLN6 gene causing a variant late infantile neuronal ceroid lipofuscinosis. | Teixeira CA | Human mutation | 2003 | PMID: 12673792 |
The gene mutated in variant late-infantile neuronal ceroid lipofuscinosis (CLN6) and in nclf mutant mice encodes a novel predicted transmembrane protein. | Wheeler RB | American journal of human genetics | 2002 | PMID: 11727201 |
Text-mined citations for rs121908080 ...
HelpRecord last updated Aug 04, 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.