NM_001127898.4(CLCN5):c.1426C>T (p.Arg476Cys) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 12, 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:: RCV001217517.8

Allele description [Variation Report for NM_001127898.4(CLCN5):c.1426C>T (p.Arg476Cys)]

NM_001127898.4(CLCN5):c.1426C>T (p.Arg476Cys)

Gene:

CLCN5:chloride voltage-gated channel 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.23

Genomic location:

Preferred name:

NM_001127898.4(CLCN5):c.1426C>T (p.Arg476Cys)

HGVS:

NC_000023.11:g.50086739C>T
NG_007159.3:g.169124C>T
NM_000084.5:c.1216C>T
NM_001127898.4:c.1426C>TMANE SELECT
NM_001127899.4:c.1426C>T
NM_001282163.2:c.1276C>T
NP_000075.1:p.Arg406Cys
NP_001121370.1:p.Arg476Cys
NP_001121371.1:p.Arg476Cys
NP_001269092.1:p.Arg426Cys
NC_000023.10:g.49851396C>T
NM_000084.4:c.1216C>T

Protein change:

R406C

Links:

dbSNP: rs782540790

NCBI 1000 Genomes Browser:

rs782540790

Molecular consequence:

NM_000084.5:c.1216C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127898.4:c.1426C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001127899.4:c.1426C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282163.2:c.1276C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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cytochrome oxidase subunit 1, partial (mitochondrion) [Luquetia lobella]
cytochrome oxidase subunit 1, partial (mitochondrion) [Luquetia lobella]
gi|312849284|gb|ADR07762.1|

Protein
Human DNA sequence from clone RP11-245K15 on chromosome 10, complete sequence
Human DNA sequence from clone RP11-245K15 on chromosome 10, complete sequence
gi|20067436|emb|AL450307.18|

Nucleotide
PREDICTED: Cucurbita pepo subsp. pepo lectin-domain containing receptor kinase V...
PREDICTED: Cucurbita pepo subsp. pepo lectin-domain containing receptor kinase VI.4-like (LOC111790130), mRNA
gi|1333105601|ref|XM_023670957.1|

Nucleotide
LOC129661473 [Homo sapiens]
LOC129661473 [Homo sapiens]
Gene ID:129661473

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001389360	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 12, 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

SCV001389360

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 12, 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, SCV001389360.5

#	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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 946618). This variant has not been reported in the literature in individuals affected with CLCN5-related conditions. This variant is present in population databases (rs782540790, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 406 of the CLCN5 protein (p.Arg406Cys).

#	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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