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NM_001127898.4(CLCN5):c.1420G>A (p.Glu474Lys) AND X-linked recessive nephrolithiasis with renal failure

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 31, 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:
RCV002471879.1

Allele description [Variation Report for NM_001127898.4(CLCN5):c.1420G>A (p.Glu474Lys)]

NM_001127898.4(CLCN5):c.1420G>A (p.Glu474Lys)

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.1420G>A (p.Glu474Lys)
HGVS:
  • NC_000023.11:g.50086733G>A
  • NG_007159.3:g.169118G>A
  • NM_000084.5:c.1210G>A
  • NM_001127898.4:c.1420G>AMANE SELECT
  • NM_001127899.4:c.1420G>A
  • NM_001282163.2:c.1270G>A
  • NP_000075.1:p.Glu404Lys
  • NP_001121370.1:p.Glu474Lys
  • NP_001121371.1:p.Glu474Lys
  • NP_001269092.1:p.Glu424Lys
  • NC_000023.10:g.49851390G>A
  • NM_001127898.3:c.1420G>A
  • NR_073607.1:n.1501G>A
Protein change:
E404K
Molecular consequence:
  • NM_000084.5:c.1210G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127898.4:c.1420G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127899.4:c.1420G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282163.2:c.1270G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
X-linked recessive nephrolithiasis with renal failure (XRN)
Synonyms:
NEPHROLITHIASIS 1; NEPHROLITHIASIS, X-LINKED RECESSIVE, TYPE 1; UROLITHIASIS, X-LINKED RECESSIVE, TYPE 1
Identifiers:
MONDO: MONDO:0010687; MedGen: C0403720; Orphanet: 1652; Orphanet: 93622; OMIM: 310468

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002767482Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Mar 31, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Novel truncating mutations in the ClC-5 chloride channel gene in patients with Dent's disease.

Carballo-Trujillo I, Garcia-Nieto V, Moya-Angeler FJ, Antón-Gamero M, Loris C, Méndez-Alvarez S, Claverie-Martin F.

Nephrol Dial Transplant. 2003 Apr;18(4):717-23.

PubMed [citation]
PMID:
12637640

Dent disease: Same CLCN5 mutation but different phenotypes in two brothers in China.

Zhang H, Wang F, Xiao H, Yao Y.

Intractable Rare Dis Res. 2017 May;6(2):114-118. doi: 10.5582/irdr.2017.01019.

PubMed [citation]
PMID:
28580211
PMCID:
PMC5451742
See all PubMed Citations (3)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002767482.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3C. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with nephrolithiasis, type I (MIM#310468). (I) 0109 - This gene is associated with X-linked recessive disease. Dent disease (MIM#300009) is now the generally accepted name for a group of hereditary tubular disorders including X-linked recessive nephrolithiasis type I (MIM#310468), hypophosphataemic rickets (MIM#300554), and low molecular weight proteinuria with hypercalciuric nephrocalcinosis (MIM#308990) (PMID: 12637640). Dent disease (MIM#300009) mainly affects males, however female carriers may show a milder phenotype (PMID: 28580211). (I) 0115 - Variants in this gene are known to have variable expressivity. The phenotype can be variable within and between families (PMID: 28580211). (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamic acid to lysine. (I) 0253 - This variant is hemizygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools or not conserved in placental mammals with a minor amino acid change. (SB) 0600 - Variant is located in the annotated voltage CLC domain. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 12, 2024