rs750478389
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_213655.5(WNK1):c.4082G>A(p.Arg1361His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,732 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1361C) has been classified as Uncertain significance.
Frequency
Consequence
NM_213655.5 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 |
---|---|---|---|---|---|---|---|
WNK1 | NM_213655.5 | c.4082G>A | p.Arg1361His | missense_variant | 14/28 | ENST00000340908.9 | |
WNK1 | NM_018979.4 | c.3326G>A | p.Arg1109His | missense_variant | 14/28 | ENST00000315939.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNK1 | ENST00000340908.9 | c.4082G>A | p.Arg1361His | missense_variant | 14/28 | 5 | NM_213655.5 | A2 | |
WNK1 | ENST00000315939.11 | c.3326G>A | p.Arg1109His | missense_variant | 14/28 | 1 | NM_018979.4 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250634Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135514
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461732Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 727162
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Pseudohypoaldosteronism type 2C;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 17, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 471178). This variant has not been reported in the literature in individuals affected with WNK1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1361 of the WNK1 protein (p.Arg1361His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at