X-54198354-A-G

Variant names:

• chrX-54198354-A-G
• rs782161434
• ENST00000354646.7:c.5373T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The ENST00000354646.7(WNK3):​c.5373T>C​(p.Asn1791Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000268 in 111,810 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 2 hem., cov: 22)
  • Exomes 𝑓: 0.0000027 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: WNK3 ENST00000354646.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.790
• Publications: 0 publications found

Genes affected

WNK3 (HGNC:14543): (WNK lysine deficient protein kinase 3) This gene encodes a protein belonging to the 'with no lysine' family of serine-threonine protein kinases. These family members lack the catalytic lysine in subdomain II, and instead have a conserved lysine in subdomain I. This family member functions as a positive regulator of the transcellular Ca2+ transport pathway, and it plays a role in the increase of cell survival in a caspase-3-dependent pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

WNK3 Gene-Disease associations (from GenCC):

• Prieto syndrome

  Inheritance: XL Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant X-54198354-A-G is Benign according to our data. Variant chrX-54198354-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 757651.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.79 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK3	NM_020922.5	c.5373T>C	p.Asn1791Asn	synonymous_variant	Exon 24 of 24		NP_065973.2
WNK3	NM_001002838.4	c.5202T>C	p.Asn1734Asn	synonymous_variant	Exon 23 of 23		NP_001002838.1
WNK3	NM_001395166.1	c.5202T>C	p.Asn1734Asn	synonymous_variant	Exon 23 of 23		NP_001382095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNK3	ENST00000354646.7	c.5373T>C	p.Asn1791Asn	synonymous_variant	Exon 24 of 24	1		ENSP00000346667.2
WNK3	ENST00000375169.7	c.5202T>C	p.Asn1734Asn	synonymous_variant	Exon 23 of 23	5		ENSP00000364312.3

Frequencies

GnomAD3 genomes AF: 0.0000268 AC: 3 AN: 111810 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000975

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000573 AC: 10 AN: 174430 AF XY: 0.00

Gnomad AFR exome AF: 0.000156

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000390

Gnomad NFE exome AF: 0.0000256

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000275 AC: 3 AN: 1092642 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 358732

African (AFR) AF: 0.000114 AC: 3 AN: 26365

American (AMR) AF: 0.00 AC: 0 AN: 34914

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19127

East Asian (EAS) AF: 0.00 AC: 0 AN: 30109

South Asian (SAS) AF: 0.00 AC: 0 AN: 52776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4111

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 839140

Other (OTH) AF: 0.00 AC: 0 AN: 45866

GnomAD4 genome AF: 0.0000268 AC: 3 AN: 111810 Hom.: 0 Cov.: 22 AF XY: 0.0000589 AC XY: 2 AN XY: 33970

African (AFR) AF: 0.0000975 AC: 3 AN: 30783

American (AMR) AF: 0.00 AC: 0 AN: 10496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3571

South Asian (SAS) AF: 0.00 AC: 0 AN: 2658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53171

Other (OTH) AF: 0.00 AC: 0 AN: 1495

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.2
DANN	Benign	0.68
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs782161434; hg19: chrX-54224787;