12-862125-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_018979.4(WNK1):c.1994C>T(p.Thr665Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0659 in 1,613,962 control chromosomes in the GnomAD database, including 3,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_018979.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WNK1 | ENST00000340908.9 | c.1994C>T | p.Thr665Ile | missense_variant | Exon 8 of 28 | 5 | NM_213655.5 | ENSP00000341292.5 | ||
WNK1 | ENST00000315939.11 | c.1994C>T | p.Thr665Ile | missense_variant | Exon 8 of 28 | 1 | NM_018979.4 | ENSP00000313059.6 |
Frequencies
GnomAD3 genomes AF: 0.0557 AC: 8471AN: 152050Hom.: 308 Cov.: 32
GnomAD3 exomes AF: 0.0661 AC: 16604AN: 251344Hom.: 652 AF XY: 0.0656 AC XY: 8905AN XY: 135834
GnomAD4 exome AF: 0.0670 AC: 97886AN: 1461794Hom.: 3546 Cov.: 32 AF XY: 0.0665 AC XY: 48390AN XY: 727202
GnomAD4 genome AF: 0.0556 AC: 8463AN: 152168Hom.: 307 Cov.: 32 AF XY: 0.0552 AC XY: 4107AN XY: 74374
ClinVar
Submissions by phenotype
not specified Benign:5
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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not provided Benign:2
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Pseudohypoaldosteronism type 2C Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Neuropathy, hereditary sensory and autonomic, type 2A Benign:1
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Pseudohypoaldosteronism type 2C;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at