rs1554434814
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_000083.3(CLCN1):c.547T>C(p.Ser183Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. S183S) has been classified as Likely benign.
Frequency
Consequence
NM_000083.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLCN1 | NM_000083.3 | c.547T>C | p.Ser183Pro | missense_variant | 4/23 | ENST00000343257.7 | |
CLCN1 | NR_046453.2 | n.649T>C | non_coding_transcript_exon_variant | 4/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLCN1 | ENST00000343257.7 | c.547T>C | p.Ser183Pro | missense_variant | 4/23 | 1 | NM_000083.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151880Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151880Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74162
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 15, 2016 | - - |
Congenital myotonia, autosomal recessive form;C2936781:Congenital myotonia, autosomal dominant form Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 15, 2020 | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CLCN1 protein function. This variant has been observed in individual(s) with autosomal dominant myotonia congenita (PMID: 23113340). ClinVar contains an entry for this variant (Variation ID: 447068). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with proline at codon 183 of the CLCN1 protein (p.Ser183Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline. 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. - |
Congenital myotonia, autosomal dominant form Uncertain:1
Uncertain significance, no assertion criteria provided | research | Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences | Apr 06, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at