NM_001042432.2(CLN3):c.771G>C (p.Glu257Asp) AND Neuronal ceroid lipofuscinosis

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 1, 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:: RCV001069649.8

Allele description [Variation Report for NM_001042432.2(CLN3):c.771G>C (p.Glu257Asp)]

NM_001042432.2(CLN3):c.771G>C (p.Glu257Asp)

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.771G>C (p.Glu257Asp)

HGVS:

NC_000016.10:g.28484025C>G
NG_008654.2:g.13278G>C
NM_000086.2:c.771G>C
NM_001042432.2:c.771G>CMANE SELECT
NM_001286104.2:c.699G>C
NM_001286105.2:c.471G>C
NM_001286109.2:c.537G>C
NM_001286110.2:c.609G>C
NP_000077.1:p.Glu257Asp
NP_001035897.1:p.Glu257Asp
NP_001035897.1:p.Glu257Asp
NP_001273033.1:p.Glu233Asp
NP_001273034.1:p.Glu157Asp
NP_001273038.1:p.Glu179Asp
NP_001273039.1:p.Glu203Asp
LRG_689t1:c.771G>C
LRG_689t2:c.771G>C
LRG_689:g.13278G>C
LRG_689p1:p.Glu257Asp
LRG_689p2:p.Glu257Asp
NC_000016.9:g.28495346C>G
NM_001042432.1:c.771G>C
NM_001042432.2:c.771G>C

Protein change:

E157D

Links:

dbSNP: rs73533466

NCBI 1000 Genomes Browser:

rs73533466

Molecular consequence:

NM_000086.2:c.771G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001042432.2:c.771G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001286104.2:c.699G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001286105.2:c.471G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001286109.2:c.537G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001286110.2:c.609G>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
SCV001234832	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001452335	Natera, Inc.	no assertion criteria provided	Uncertain significance (Sep 16, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001234832

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2021)

germline

clinical testing

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

SCV001452335

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Sep 16, 2020)

germline

clinical testing

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, SCV001234832.4

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

Description

This sequence change replaces glutamic acid with aspartic acid at codon 257 of the CLN3 protein (p.Glu257Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CLN3-related conditions. ClinVar contains an entry for this variant (Variation ID: 497479). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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

From Natera, Inc., SCV001452335.1

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

#	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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