rs774954731
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_213655.5(WNK1):c.5230G>A(p.Val1744Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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. V1744V) has been classified as Likely benign.
Frequency
Consequence
NM_213655.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNK1 | NM_213655.5 | c.5230G>A | p.Val1744Ile | missense_variant | 19/28 | ENST00000340908.9 | |
WNK1 | NM_018979.4 | c.4474G>A | p.Val1492Ile | missense_variant | 19/28 | ENST00000315939.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNK1 | ENST00000340908.9 | c.5230G>A | p.Val1744Ile | missense_variant | 19/28 | 5 | NM_213655.5 | A2 | |
WNK1 | ENST00000315939.11 | c.4474G>A | p.Val1492Ile | missense_variant | 19/28 | 1 | NM_018979.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251034Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135644
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461886Hom.: 0 Cov.: 81 AF XY: 0.00000413 AC XY: 3AN XY: 727244
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74310
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 11, 2022 | The p.V1744I variant (also known as c.5230G>A), located in coding exon 19 of the WNK1 gene, results from a G to A substitution at nucleotide position 5230. The valine at codon 1744 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Pseudohypoaldosteronism type 2C;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 28, 2021 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with WNK1-related disease. ClinVar contains an entry for this variant (Variation ID: 471189). This variant is present in population databases (rs774954731, ExAC 0.01%). This sequence change replaces valine with isoleucine at codon 1492 of the WNK1 protein (p.Val1492Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at