1-16022691-CT-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004070.4(CLCNKA):c.73del(p.Cys25ValfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,552,854 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CLCNKA
NM_004070.4 frameshift
NM_004070.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.573
Genes affected
CLCNKA (HGNC:2026): (chloride voltage-gated channel Ka) This gene is a member of the CLC family of voltage-gated chloride channels. The encoded protein is predicted to have 12 transmembrane domains, and requires a beta subunit called barttin to form a functional channel. It is thought to function in salt reabsorption in the kidney and potassium recycling in the inner ear. The gene is highly similar to CLCNKB, which is located 10 kb downstream from this gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CLCNKA | NM_004070.4 | c.73del | p.Cys25ValfsTer15 | frameshift_variant | 2/20 | ENST00000331433.5 | NP_004061.3 | |
| CLCNKA | NM_001042704.2 | c.73del | p.Cys25ValfsTer15 | frameshift_variant | 2/20 | NP_001036169.1 | ||
| CLCNKA | NM_001257139.2 | c.73del | p.Cys25ValfsTer15 | frameshift_variant | 2/19 | NP_001244068.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CLCNKA | ENST00000331433.5 | c.73del | p.Cys25ValfsTer15 | frameshift_variant | 2/20 | 1 | NM_004070.4 | ENSP00000332771 | P4 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000143 AC: 2AN: 1400708Hom.: 0 Cov.: 30 AF XY: 0.00000289 AC XY: 2AN XY: 691700
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GnomAD4 genome 0.00000657 AC: 1AN: 152146Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74322
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not provided Uncertain:1
| Uncertain significance, no assertion criteria provided | research | Gharavi Laboratory, Columbia University | Sep 16, 2018 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at