NM_001042432.2(CLN3):c.196A>C (p.Lys66Gln) AND Neuronal ceroid lipofuscinosis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 5, 2022
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:: RCV002861357.3

Allele description [Variation Report for NM_001042432.2(CLN3):c.196A>C (p.Lys66Gln)]

NM_001042432.2(CLN3):c.196A>C (p.Lys66Gln)

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.196A>C (p.Lys66Gln)

HGVS:

NC_000016.10:g.28489316T>G
NG_008654.2:g.7987A>C
NM_000086.2:c.196A>C
NM_001042432.2:c.196A>CMANE SELECT
NM_001286104.2:c.196A>C
NM_001286105.2:c.-25A>C
NM_001286109.2:c.34A>C
NM_001286110.2:c.34A>C
NP_000077.1:p.Lys66Gln
NP_001035897.1:p.Lys66Gln
NP_001035897.1:p.Lys66Gln
NP_001273033.1:p.Lys66Gln
NP_001273038.1:p.Lys12Gln
NP_001273039.1:p.Lys12Gln
LRG_689t1:c.196A>C
LRG_689t2:c.196A>C
LRG_689:g.7987A>C
LRG_689p1:p.Lys66Gln
LRG_689p2:p.Lys66Gln
NC_000016.9:g.28500637T>G
NM_001042432.1:c.196A>C

Protein change:

K12Q

Molecular consequence:

NM_001286105.2:c.-25A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000086.2:c.196A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001042432.2:c.196A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001286104.2:c.196A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001286109.2:c.34A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001286110.2:c.34A>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV003216533	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 5, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003216533

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 5, 2022)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003216533.2

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with CLN3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 66 of the CLN3 protein (p.Lys66Gln).

#	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: Sep 29, 2024

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