NM_017882.3(CLN6):c.486+1G>C AND Neuronal ceroid lipofuscinosis

Clinical significance:Likely pathogenic (Last evaluated: Jul 21, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_017882.3(CLN6):c.486+1G>C]


CLN6:CLN6 transmembrane ER protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
  • NC_000015.10:g.68211674C>G
  • NG_008764.2:g.50538G>C
  • NM_017882.3:c.486+1G>CMANE SELECT
  • LRG_832t1:c.486+1G>C
  • LRG_832:g.50538G>C
  • NC_000015.9:g.68504012C>G
Molecular consequence:
  • NM_017882.3:c.486+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]


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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001574272Invitaecriteria provided, single submitter
Likely pathogenic
(Jul 21, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Novel mutations in the CLN6 gene causing a variant late infantile neuronal ceroid lipofuscinosis.

Teixeira CA, Espinola J, Huo L, Kohlschütter J, Persaud Sawin DA, Minassian B, Bessa CJ, Guimarães A, Stephan DA, Sá Miranda MC, MacDonald ME, Ribeiro MG, Boustany RM.

Hum Mutat. 2003 May;21(5):502-8.

PubMed [citation]

Kufs disease due to mutation of CLN6: clinical, pathological and molecular genetic features.

Berkovic SF, Oliver KL, Canafoglia L, Krieger P, Damiano JA, Hildebrand MS, Morbin M, Vears DF, Sofia V, Giuliano L, Garavaglia B, Simonati A, Santorelli FM, Gambardella A, Labate A, Belcastro V, Castellotti B, Ozkara C, Zeman A, Rankin J, Mole SE, Aguglia U, et al.

Brain. 2019 Jan 1;142(1):59-69. doi: 10.1093/brain/awy297.

PubMed [citation]
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001574272.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)


This sequence change affects a donor splice site in intron 4 of the CLN6 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individual(s) with neuronal ceroid lipofuscinosis type 6 (PMID: 12673792, 30561534). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CLN6 are known to be pathogenic (PMID: 19135028). 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.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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