chr17-42795479-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_032387.5(WNK4):c.2980C>T(p.Arg994Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,614,126 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R994Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_032387.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNK4 | NM_032387.5 | c.2980C>T | p.Arg994Trp | missense_variant | 15/19 | ENST00000246914.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNK4 | ENST00000246914.10 | c.2980C>T | p.Arg994Trp | missense_variant | 15/19 | 1 | NM_032387.5 | P1 | |
WNK4 | ENST00000591448.5 | c.*1481C>T | 3_prime_UTR_variant, NMD_transcript_variant | 14/18 | 1 | ||||
WNK4 | ENST00000587745.1 | c.71-146C>T | intron_variant | 5 | |||||
COA3 | ENST00000586680.1 | c.*817G>A | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152234Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251436Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135890
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461892Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3AN XY: 727248
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152234Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74378
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 04, 2024 | The c.2980C>T (p.R994W) alteration is located in exon 15 (coding exon 15) of the WNK4 gene. This alteration results from a C to T substitution at nucleotide position 2980, causing the arginine (R) at amino acid position 994 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at