rs765895186
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000085.5(CLCNKB):āc.1375A>Cā(p.Asn459His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000985 in 1,613,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_000085.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLCNKB | NM_000085.5 | c.1375A>C | p.Asn459His | missense_variant | 14/20 | ENST00000375679.9 | |
CLCNKB | NM_001165945.2 | c.868A>C | p.Asn290His | missense_variant | 7/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLCNKB | ENST00000375679.9 | c.1375A>C | p.Asn459His | missense_variant | 14/20 | 1 | NM_000085.5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152066Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000798 AC: 20AN: 250662Hom.: 0 AF XY: 0.0000885 AC XY: 12AN XY: 135586
GnomAD4 exome AF: 0.0000972 AC: 142AN: 1461612Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 78AN XY: 727146
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152066Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74306
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 08, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2023 | 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. 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 not expected to disrupt CLCNKB protein function. ClinVar contains an entry for this variant (Variation ID: 585701). This variant has not been reported in the literature in individuals affected with CLCNKB-related conditions. This variant is present in population databases (rs765895186, gnomAD 0.02%). This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 459 of the CLCNKB protein (p.Asn459His). - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 24, 2022 | The c.1375A>C (p.N459H) alteration is located in exon 14 (coding exon 13) of the CLCNKB gene. This alteration results from a A to C substitution at nucleotide position 1375, causing the asparagine (N) at amino acid position 459 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Bartter disease type 3;C4310805:Bartter disease type 4B Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 14, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at