12-879688-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_018979.4(WNK1):c.2489C>T(p.Pro830Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P830P) has been classified as Likely benign.
Frequency
Consequence
NM_018979.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNK1 | NM_018979.4 | c.2489C>T | p.Pro830Leu | missense_variant | 11/28 | ENST00000315939.11 | |
WNK1 | NM_213655.5 | c.3867+1327C>T | intron_variant | ENST00000340908.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNK1 | ENST00000315939.11 | c.2489C>T | p.Pro830Leu | missense_variant | 11/28 | 1 | NM_018979.4 | P2 | |
WNK1 | ENST00000340908.9 | c.3867+1327C>T | intron_variant | 5 | NM_213655.5 | A2 |
Frequencies
GnomAD3 genomes AF: 0.00000659 AC: 1AN: 151786Hom.: 0 Cov.: 29
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251450Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135898
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461868Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3AN XY: 727242
GnomAD4 genome AF: 0.00000659 AC: 1AN: 151786Hom.: 0 Cov.: 29 AF XY: 0.0000135 AC XY: 1AN XY: 74138
ClinVar
Submissions by phenotype
Pseudohypoaldosteronism type 2C;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2017 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with WNK1-related disease. This variant is present in population databases (rs575889688, ExAC 0.001%). This sequence change replaces proline with leucine at codon 830 of the WNK1 protein (p.Pro830Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at