NM_001042432.2(CLN3):c.1028G>A (p.Arg343His) AND Neuronal ceroid lipofuscinosis

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 16, 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:: RCV001248053.3

Allele description [Variation Report for NM_001042432.2(CLN3):c.1028G>A (p.Arg343His)]

NM_001042432.2(CLN3):c.1028G>A (p.Arg343His)

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.1028G>A (p.Arg343His)

Other names:

p.R343H:CGT>CAT

HGVS:

NC_000016.10:g.28482133C>T
NG_008654.2:g.15170G>A
NM_000086.2:c.1028G>A
NM_001042432.2:c.1028G>AMANE SELECT
NM_001286104.2:c.956G>A
NM_001286105.2:c.728G>A
NM_001286109.2:c.794G>A
NM_001286110.2:c.866G>A
NP_000077.1:p.Arg343His
NP_001035897.1:p.Arg343His
NP_001035897.1:p.Arg343His
NP_001273033.1:p.Arg319His
NP_001273034.1:p.Arg243His
NP_001273038.1:p.Arg265His
NP_001273039.1:p.Arg289His
LRG_689t1:c.1028G>A
LRG_689t2:c.1028G>A
LRG_689:g.15170G>A
LRG_689p1:p.Arg343His
LRG_689p2:p.Arg343His
NC_000016.9:g.28493454C>T
NM_001042432.1:c.1028G>A
NM_001042432.2:c.1028G>A

Protein change:

R243H

Links:

dbSNP: rs771305783

NCBI 1000 Genomes Browser:

rs771305783

Molecular consequence:

NM_000086.2:c.1028G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001042432.2:c.1028G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001286104.2:c.956G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001286105.2:c.728G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001286109.2:c.794G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001286110.2:c.866G>A - 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
SCV001421515	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 16, 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

SCV001421515

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 16, 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, SCV001421515.2

#	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 arginine, which is basic and polar, with histidine, which is basic and polar, at codon 343 of the CLN3 protein (p.Arg343His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 205096). 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 histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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

Last Updated: Sep 29, 2024

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