17-42795167-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_032387.5(WNK4):c.2746C>T(p.Pro916Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000427 in 1,614,058 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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. P916L) has been classified as Uncertain significance.
Frequency
Consequence
NM_032387.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.2746C>T | p.Pro916Ser | missense_variant | 14/19 | ENST00000246914.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNK4 | ENST00000246914.10 | c.2746C>T | p.Pro916Ser | missense_variant | 14/19 | 1 | NM_032387.5 | P1 | |
WNK4 | ENST00000591448.5 | c.*1247C>T | 3_prime_UTR_variant, NMD_transcript_variant | 13/18 | 1 | ||||
WNK4 | ENST00000587745.1 | c.71-458C>T | intron_variant | 5 | |||||
COA3 | ENST00000586680.1 | c.*1129G>A | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152052Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000103 AC: 26AN: 251456Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135900
GnomAD4 exome AF: 0.0000445 AC: 65AN: 1461888Hom.: 1 Cov.: 36 AF XY: 0.0000550 AC XY: 40AN XY: 727246
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152170Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74396
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 27, 2022 | The c.2746C>T (p.P916S) alteration is located in exon 14 (coding exon 14) of the WNK4 gene. This alteration results from a C to T substitution at nucleotide position 2746, causing the proline (P) at amino acid position 916 to be replaced by a serine (S). 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