rs754320383
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_018979.4(WNK1):c.2942C>T(p.Pro981Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P981P) has been classified as Likely benign.
Frequency
Consequence
NM_018979.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNK1 | NM_018979.4 | c.2942C>T | p.Pro981Leu | missense_variant | 12/28 | ENST00000315939.11 | |
WNK1 | NM_213655.5 | c.3868-862C>T | intron_variant | ENST00000340908.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNK1 | ENST00000315939.11 | c.2942C>T | p.Pro981Leu | missense_variant | 12/28 | 1 | NM_018979.4 | P2 | |
WNK1 | ENST00000340908.9 | c.3868-862C>T | intron_variant | 5 | NM_213655.5 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152016Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251476Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135914
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461894Hom.: 0 Cov.: 33 AF XY: 0.0000220 AC XY: 16AN XY: 727248
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152016Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74234
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 | Labcorp Genetics (formerly Invitae), Labcorp | Jul 21, 2018 | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This sequence change replaces proline with leucine at codon 981 of the WNK1 protein (p.Pro981Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs754320383, ExAC 0.001%). This variant has not been reported in the literature in individuals with WNK1-related disease. 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