rs1201537831

Positions:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_213655.5(WNK1):ā€‹c.4704A>Cā€‹(p.Thr1568=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,890 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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000096 ( 0 hom. )

Consequence

WNK1
NM_213655.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.24
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 -7 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 12-884752-A-C is Benign according to our data. Variant chr12-884752-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 538545.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.24 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WNK1NM_213655.5 linkuse as main transcriptc.4704A>C p.Thr1568= synonymous_variant 19/28 ENST00000340908.9 NP_998820.3
WNK1NM_018979.4 linkuse as main transcriptc.3948A>C p.Thr1316= synonymous_variant 19/28 ENST00000315939.11 NP_061852.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WNK1ENST00000340908.9 linkuse as main transcriptc.4704A>C p.Thr1568= synonymous_variant 19/285 NM_213655.5 ENSP00000341292 A2Q9H4A3-5
WNK1ENST00000315939.11 linkuse as main transcriptc.3948A>C p.Thr1316= synonymous_variant 19/281 NM_018979.4 ENSP00000313059 P2Q9H4A3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461890
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Pseudohypoaldosteronism type 2C;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 26, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
CADD
Benign
6.4
DANN
Benign
0.70
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs1201537831; hg19: chr12-993918; API