NM_017882.3(CLN6):c.307C>T (p.Arg103Trp) AND Ceroid lipofuscinosis, neuronal, 6A

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Oct 2, 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:: RCV000678437.3

Allele description [Variation Report for NM_017882.3(CLN6):c.307C>T (p.Arg103Trp)]

NM_017882.3(CLN6):c.307C>T (p.Arg103Trp)

Gene:

CLN6:CLN6 transmembrane ER protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q23

Genomic location:

Preferred name:

NM_017882.3(CLN6):c.307C>T (p.Arg103Trp)

HGVS:

NC_000015.10:g.68211854G>A
NG_008764.2:g.50358C>T
NM_017882.3:c.307C>TMANE SELECT
NP_060352.1:p.Arg103Trp
LRG_832t1:c.307C>T
LRG_832:g.50358C>T
LRG_832p1:p.Arg103Trp
NC_000015.9:g.68504192G>A
NM_017882.2:c.307C>T

Protein change:

R103W

Links:

dbSNP: rs201095412

NCBI 1000 Genomes Browser:

rs201095412

Molecular consequence:

NM_017882.3:c.307C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Ceroid lipofuscinosis, neuronal, 6A
Synonyms:: Neuronal ceroid lipofuscinosis, Gypsy/Indian early juvenile variant; Neuronal ceroid lipofuscinosis 6; CLN6-Related Neuronal Ceroid-Lipofuscinosis
Identifiers:: MONDO: MONDO:0011144; MedGen: C5551375; Orphanet: 168491; OMIM: 601780

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000804303	Translational Research Program on Neuronal Ceroid Lipofuscinosis, Center for the Study of Inborn Errors of Metabolism	no assertion criteria provided	Pathogenic	inherited	research
SCV002012075	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 2, 2021)	paternal	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30561534, 27903347, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000804303

Translational Research Program on Neuronal Ceroid Lipofuscinosis, Center for the Study of Inborn Errors of Metabolism

no assertion criteria provided

Pathogenic

inherited

research

SCV002012075

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 2, 2021)

paternal

clinical testing

PubMed (3)
[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	inherited	yes	1	not provided	not provided	not provided	not provided	research
not provided	paternal	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

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]

PMID:: 30561534

[Clinical, genetic and pathological features of neuronal ceroid lipofuscinosis in 5 Chinese patients].

Ren SC, Gao BQ, Wang YJ, Wu XJ, Tian ZX, Sun YL.

Zhonghua Yi Xue Za Zhi. 2016 Nov 22;96(43):3504-3507. doi: 10.3760/cma.j.issn.0376-2491.2016.43.013. Chinese.

PubMed [citation]

PMID:: 27903347

See all PubMed Citations (3)

Details of each submission

From Translational Research Program on Neuronal Ceroid Lipofuscinosis, Center for the Study of Inborn Errors of Metabolism, SCV000804303.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	not provided

Description

Late Infantile NCL / Kufs disease

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From 3billion, SCV002012075.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

Description

Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with supporting evidence (ClinVar ID: VCV000498240.4, PS1_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.0000426, PM2). A different missense change at the same codon (p.Arg103Gln) has been reported as pathogenic (PMID: 30561534, 27903347, PM5). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.926, 3Cnet: 0.941, PP3). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	paternal	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine