rs921731349
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP7
The NM_000083.3(CLCN1):c.432G>A(p.Gln144=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000083.3 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLCN1 | NM_000083.3 | c.432G>A | p.Gln144= | splice_region_variant, synonymous_variant | 3/23 | ENST00000343257.7 | |
CLCN1 | NR_046453.2 | n.534G>A | splice_region_variant, non_coding_transcript_exon_variant | 3/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLCN1 | ENST00000343257.7 | c.432G>A | p.Gln144= | splice_region_variant, synonymous_variant | 3/23 | 1 | NM_000083.3 | P4 | |
CLCN1 | ENST00000432192.6 | c.201G>A | p.Gln67= | splice_region_variant, synonymous_variant, NMD_transcript_variant | 2/23 | 1 | |||
CLCN1 | ENST00000650516.2 | c.432G>A | p.Gln144= | splice_region_variant, synonymous_variant | 3/23 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152102Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461830Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8AN XY: 727222
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152102Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74290
ClinVar
Submissions by phenotype
Congenital myotonia, autosomal recessive form;C2936781:Congenital myotonia, autosomal dominant form Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 11, 2019 | This sequence change affects codon 144 of the CLCN1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CLCN1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CLCN1-related disease. ClinVar contains an entry for this variant (Variation ID: 531759). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at