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NM_017882.3(CLN6):c.311C>T (p.Ser104Phe) AND Ceroid lipofuscinosis, neuronal, 6A

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 19, 2023
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:
RCV003388608.2

Allele description [Variation Report for NM_017882.3(CLN6):c.311C>T (p.Ser104Phe)]

NM_017882.3(CLN6):c.311C>T (p.Ser104Phe)

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.311C>T (p.Ser104Phe)
HGVS:
  • NC_000015.10:g.68211850G>A
  • NG_008764.2:g.50362C>T
  • NM_017882.2:c.311C>T
  • NM_017882.3:c.311C>TMANE SELECT
  • NP_060352.1:p.Ser104Phe
  • LRG_832t1:c.311C>T
  • LRG_832:g.50362C>T
  • LRG_832p1:p.Ser104Phe
  • NC_000015.9:g.68504188G>A
Protein change:
S104F
Links:
dbSNP: rs777921628
NCBI 1000 Genomes Browser:
rs777921628
Molecular consequence:
  • NM_017882.3:c.311C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004100319Human Genome Lab, NIMHANS, National Institute of Mental Health and Neuro Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Oct 19, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
South Indian Hindugermlineyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Human Genome Lab, NIMHANS, National Institute of Mental Health and Neuro Sciences, SCV004100319.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1South Indian Hindu1not providednot providedclinical testing PubMed (1)

Description

12 years old male born of consanguineous parentage presented with h/o regression of milestones, ataxia, and spasticity. His father and all siblings had developmental delay, mainly language. On examination, he had ocular telangiectasia, ataxia, mild spasticity. MRI Brain showed hypointense thalami, periventricular white matter paucity with hyperintensities and diffuse cerebral and cerebellar atrophy. The NM_017882.3:c.311C>T variant was observed in this individual in homozygous state, confirming the diagnosis.

Description

The missense variant NM_017882.3(CLN6):c.311C>T is a previously reported variant of uncertain significance (ClinVar Accession ID: VCV001059430.5). The NP_060352.1:p.Ser104Phe variant is novel (not in any individuals) in 1000 genome, in gnomAD as well as in our inhouse database. There is a large physicochemical difference between serine and phenylalanine, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. 3 variants within 6 amino acid positions of the variant p.Ser104Phe have been shown to be pathogenic, while none have been shown to be benign. The p.Ser104Phe missense variant is predicted to be damaging by both SIFT and PolyPhen2. The nucleotide c.311 in CLN6 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. In addition, the patient’s phenotype matches with that of the disorder caused by pathogenic variants in CLN6. For these reasons, this variant has been classified as Likely Pathogenic (PM2 PM1 PP3 PP4_Moderate)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024