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NM_001829.4(CLCN3):c.755T>C (p.Ile252Thr) AND Neurodevelopmental disorder with hypotonia and brain abnormalities

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 15, 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:
RCV002051932.1

Allele description [Variation Report for NM_001829.4(CLCN3):c.755T>C (p.Ile252Thr)]

NM_001829.4(CLCN3):c.755T>C (p.Ile252Thr)

Gene:
CLCN3:chloride voltage-gated channel 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q33
Genomic location:
Preferred name:
NM_001829.4(CLCN3):c.755T>C (p.Ile252Thr)
HGVS:
  • NC_000004.12:g.169692139T>C
  • NG_029731.1:g.76619T>C
  • NM_001243372.2:c.755T>C
  • NM_001243374.2:c.674T>C
  • NM_001829.4:c.755T>CMANE SELECT
  • NM_173872.4:c.755T>C
  • NP_001230301.1:p.Ile252Thr
  • NP_001230303.2:p.Ile225Thr
  • NP_001820.2:p.Ile252Thr
  • NP_776297.2:p.Ile252Thr
  • NC_000004.11:g.170613290T>C
  • NM_001829.3:c.755T>C
Protein change:
I225T
Links:
dbSNP: rs1732397227
NCBI 1000 Genomes Browser:
rs1732397227
Molecular consequence:
  • NM_001243372.2:c.755T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243374.2:c.674T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001829.4:c.755T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_173872.4:c.755T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Neurodevelopmental disorder with hypotonia and brain abnormalities
Identifiers:
MONDO: MONDO:0859187; MedGen: C5561977; OMIM: 619512

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002319206SIB Swiss Institute of Bioinformatics
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Mar 15, 2022) 		unknowncuration

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Unique variants in CLCN3, encoding an endosomal anion/proton exchanger, underlie a spectrum of neurodevelopmental disorders.

Duncan AR, Polovitskaya MM, Gaitán-Peñas H, Bertelli S, VanNoy GE, Grant PE, O'Donnell-Luria A, Valivullah Z, Lovgren AK, England EM, Agolini E, Madden JA, Schmitz-Abe K, Kritzer A, Hawley P, Novelli A, Alfieri P, Colafati GS, Wieczorek D, Platzer K, Luppe J, Koch-Hogrebe M, et al.

Am J Hum Genet. 2021 Aug 5;108(8):1450-1465. doi: 10.1016/j.ajhg.2021.06.003. Epub 2021 Jun 28.

PubMed [citation]
PMID:
34186028
PMCID:
PMC8387284

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From SIB Swiss Institute of Bioinformatics, SCV002319206.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)

Description

This variant is interpreted as likely pathogenic for Neurodevelopmental disorder with hypotonia and brain abnormalities, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); De novo, paternity and maternity confirmed (PS2 downgraded to moderate); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3); Missense variant in a gene that has a low rate of benign missense variation (PP2).

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

Last Updated: Jun 23, 2024