NM_018941.4(CLN8):c.278C>G (p.Ala93Gly) AND Neuronal ceroid lipofuscinosis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 25, 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:: RCV002018768.5

Allele description [Variation Report for NM_018941.4(CLN8):c.278C>G (p.Ala93Gly)]

NM_018941.4(CLN8):c.278C>G (p.Ala93Gly)

Gene:

CLN8:CLN8 transmembrane ER and ERGIC protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8p23.3

Genomic location:

Preferred name:

NM_018941.4(CLN8):c.278C>G (p.Ala93Gly)

HGVS:

NC_000008.11:g.1771332C>G
NG_008656.2:g.20555C>G
NM_018941.4:c.278C>GMANE SELECT
NP_061764.2:p.Ala93Gly
LRG_691:g.20555C>G
NC_000008.10:g.1719498C>G

Protein change:

A93G

Links:

dbSNP: rs1468620144

NCBI 1000 Genomes Browser:

rs1468620144

Molecular consequence:

NM_018941.4:c.278C>G - 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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N-Acetylgalactosaminyltransferases
N-Acetylgalactosaminyltransferases
Enzymes that catalyze the transfer of N-acetylgalactosamine from a nucleoside diphosphate N-acetylgalactosamine to an acceptor molecule which is frequently another carbohydrat...<br/>Year introduced: 1993

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002264052	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 25, 2021)	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

SCV002264052

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 25, 2021)

germline

clinical testing

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

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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 Invitae, SCV002264052.3

#	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CLN8 protein function. This variant has not been reported in the literature in individuals affected with CLN8-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with glycine at codon 93 of the CLN8 protein (p.Ala93Gly). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and glycine.

#	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: Mar 5, 2024

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