rs756914631

Positions:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_018979.4(WNK1):​c.192C>T​(p.Asp64Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,612,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

WNK1
NM_018979.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.40
Variant links:
Genes affected
WNK1 (HGNC:14540): (WNK lysine deficient protein kinase 1) This gene encodes a member of the WNK subfamily of serine/threonine protein kinases. The encoded protein may be a key regulator of blood pressure by controlling the transport of sodium and chloride ions. Mutations in this gene have been associated with pseudohypoaldosteronism type II and hereditary sensory neuropathy type II. Alternatively spliced transcript variants encoding different isoforms have been described but the full-length nature of all of them has yet to be determined.[provided by RefSeq, May 2010]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 12-753757-C-T is Benign according to our data. Variant chr12-753757-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 471170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.4 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WNK1NM_213655.5 linkuse as main transcriptc.192C>T p.Asp64Asp synonymous_variant 1/28 ENST00000340908.9 NP_998820.3 Q9H4A3-5
WNK1NM_018979.4 linkuse as main transcriptc.192C>T p.Asp64Asp synonymous_variant 1/28 ENST00000315939.11 NP_061852.3 Q9H4A3-1A5D8Z4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WNK1ENST00000340908.9 linkuse as main transcriptc.192C>T p.Asp64Asp synonymous_variant 1/285 NM_213655.5 ENSP00000341292.5 Q9H4A3-5
WNK1ENST00000315939.11 linkuse as main transcriptc.192C>T p.Asp64Asp synonymous_variant 1/281 NM_018979.4 ENSP00000313059.6 Q9H4A3-1

Frequencies

GnomAD3 genomes
AF:
0.000191
AC:
29
AN:
152182
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000851
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000181
AC:
44
AN:
242734
Hom.:
0
AF XY:
0.000151
AC XY:
20
AN XY:
132430
show subpopulations
Gnomad AFR exome
AF:
0.0000643
Gnomad AMR exome
AF:
0.000785
Gnomad ASJ exome
AF:
0.000102
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000112
Gnomad OTH exome
AF:
0.000504
GnomAD4 exome
AF:
0.000127
AC:
186
AN:
1460056
Hom.:
0
Cov.:
32
AF XY:
0.000124
AC XY:
90
AN XY:
726332
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000872
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000103
Gnomad4 OTH exome
AF:
0.000447
GnomAD4 genome
AF:
0.000190
AC:
29
AN:
152300
Hom.:
0
Cov.:
33
AF XY:
0.000255
AC XY:
19
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000850
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000116
Hom.:
0
Bravo
AF:
0.000344
EpiCase
AF:
0.000218
EpiControl
AF:
0.000296

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Pseudohypoaldosteronism type 2C;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:2
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsSep 23, 2021- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
CADD
Benign
14
DANN
Benign
0.97

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs756914631; hg19: chr12-862923; API