NM_001042432.2(CLN3):c.222+5G>C AND Neuronal ceroid lipofuscinosis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 20, 2021
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:: RCV002513685.1

Allele description [Variation Report for NM_001042432.2(CLN3):c.222+5G>C]

NM_001042432.2(CLN3):c.222+5G>C

Gene:

CLN3:CLN3 lysosomal/endosomal transmembrane protein, battenin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p12.1

Genomic location:

Preferred name:

NM_001042432.2(CLN3):c.222+5G>C

HGVS:

NC_000016.10:g.28489285C>G
NG_008654.2:g.8018G>C
NM_000086.2:c.222+5G>C
NM_001042432.2:c.222+5G>CMANE SELECT
NM_001286104.2:c.222+5G>C
NM_001286105.2:c.2+5G>C
NM_001286109.2:c.60+5G>C
NM_001286110.2:c.60+5G>C
LRG_689t1:c.222+5G>C
LRG_689t2:c.222+5G>C
LRG_689:g.8018G>C
NC_000016.9:g.28500606C>G
NM_001042432.1:c.222+5G>C

Links:

dbSNP: rs386833711

NCBI 1000 Genomes Browser:

rs386833711

Molecular consequence:

NM_000086.2:c.222+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001042432.2:c.222+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001286104.2:c.222+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001286105.2:c.2+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001286109.2:c.60+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001286110.2:c.60+5G>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003443546	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 20, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21990111, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003443546

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 20, 2021)

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

Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses.

Kousi M, Lehesjoki AE, Mole SE.

Hum Mutat. 2012 Jan;33(1):42-63. doi: 10.1002/humu.21624. Epub 2011 Nov 16. Review.

PubMed [citation]

PMID:: 21990111

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV003443546.1

#	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 falls in intron 4 of the CLN3 gene. It does not directly change the encoded amino acid sequence of the CLN3 protein. It affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with neuronal ceroid lipofuscinosis type 3 (PMID: 21990111). ClinVar contains an entry for this variant (Variation ID: 56260). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Feb 18, 2023

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