U.S. flag

An official website of the United States government

NM_001830.4(CLCN4):c.1646T>C (p.Ile549Thr) AND Intellectual disability, X-linked 49

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 30, 2019
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV001253788.2

Allele description [Variation Report for NM_001830.4(CLCN4):c.1646T>C (p.Ile549Thr)]

NM_001830.4(CLCN4):c.1646T>C (p.Ile549Thr)

Gene:
CLCN4:chloride voltage-gated channel 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp22.2
Genomic location:
Preferred name:
NM_001830.4(CLCN4):c.1646T>C (p.Ile549Thr)
HGVS:
  • NC_000023.11:g.10213750T>C
  • NG_012496.1:g.61806T>C
  • NM_001256944.2:c.1364T>C
  • NM_001830.4:c.1646T>CMANE SELECT
  • NP_001243873.1:p.Ile455Thr
  • NP_001821.2:p.Ile549Thr
  • NC_000023.10:g.10181790T>C
  • NM_001830.3:c.1646T>C
  • p.Ile549Thr
Protein change:
I455T
Links:
dbSNP: rs1924631837
NCBI 1000 Genomes Browser:
rs1924631837
Molecular consequence:
  • NM_001256944.2:c.1364T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001830.4:c.1646T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Intellectual disability, X-linked 49 (MRXSRC)
Synonyms:
MRX49; MENTAL RETARDATION, X-LINKED 15; RAYNAUD-CLAES SYNDROME; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010250; MedGen: C0796221; Orphanet: 777; OMIM: 300114

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001427095Clinical Genomics Laboratory, Stanford Medicine
no assertion criteria provided
Likely pathogenic
(Oct 30, 2019) 		germlineclinical testing

Help

Summary from all submissions

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

Details of each submission

From Clinical Genomics Laboratory, Stanford Medicine, SCV001427095.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providedclinical testingnot provided

Description

The p.Ile549Thr variant in the CLCN4 gene was identified de novo in this individual, but has not been previously reported in association with disease. This variant was absent from large population databases, including the Genome Aggregation Database (http://gnomad.broadinstitute.org/). The CLCN4 gene has fewer missense variants in the general population than expected. A low rate of missense variation may suggest that this gene is intolerant to missense variation. Computational tools predict that the p.Ile549Thr variant is deleterious; however, the accuracy of in silico algorithms is limited. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Ile549Thr variant as likely pathogenic for CLCN4- associated neurodevelopmental disorder in an X-linked dominant manner based on the information above. [ACMG evidence codes used: PS2_moderate; PM2; PP2; PP3]

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

Last Updated: Jul 7, 2024