WNK1 : c.421G>A

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.421G>A	p.A141T (Ala > Thr)	substitution	missense	chr12:863152 (forward strand)	0.16333369

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.16333369 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

Detection in Population Databases

Database	European	African	East Asian	South Asian	American	Finnish	Other	Total
ExAC	0.17899651 5444 / 30414	0.03681319 134 / 3640	0.10109763 350 / 3462	0.17394481 2143 / 12320	0.09609455 374 / 3892	0.30150309 682 / 2262	0.20673077 86 / 416	0.16333369 9213 / 56406
ESP	0.10793 896 / 8302	0.02545 107 / 4204						0.08020 1003 / 12506
1KG	0.12129 98 / 808	0.01664 22 / 1322	0.06647 67 / 1008	0.11656 114 / 978	0.05331 37 / 694	0.17677 35 / 198		0.07448 373 / 5008

View sub-population details for 1000 Genomes (1KG) data

Hide sub-population details for 1000 Genomes (1KG) data

0.14286 26 / 182 British	0.02459 3 / 122 African-American	0.13978 26 / 186 Chinese Dai	0.09884 17 / 172 Bengali	0.06383 12 / 188 Colombian
0.12617 27 / 214 Iberian	0.02083 4 / 192 African-Caribbean	0.03398 7 / 206 Han, Beijing	0.09223 19 / 206 Gujarati Indian	0.04688 6 / 128 Mexican, LA
0.11682 25 / 214 Toscani	0.00505 1 / 198 Esan, Nigeria	0.02885 6 / 208 Japanese	0.12255 25 / 204 Indian Telugu	0.02353 4 / 170 Peruvian
0.10101 20 / 198 Utah Europeans	0.02212 5 / 226 Gambian	0.05556 11 / 198 Kinh, Vietnam	0.15625 30 / 192 Punjabi, Lahore	0.07212 15 / 208 Puerto Rican
	0.02525 5 / 198 Luhya, Kenya	0.08095 17 / 210 Southern Han	0.11275 23 / 204 Tamil
	0.02353 4 / 170 Mende
	0.00000 0 / 216 Yoruba, Nigeria

The Exome Aggregation Consortium (ExAC) is a database of 60,706 unrelated individuals sequenced as part of various disease-specific and population genetic studies. There is partial overlap between ExAC and 1000 Genomes (1KG) (1,851 of the 2,504 samples in 1KG) and the Exome Sequencing Project (ESP) (3,936 of the 6,500 samples in ESP).

Other Variant & Gene Details

Canonical Sequences
Transcript	ENST00000315939		NM_018979.3
Protein	ENSP00000313059			Q9H4A3

Missense Variant Predictions
SIFT	Grantham	Polyphen-DIV	Polyphen-VAR	Summary 12.5% of algorithms have predicted that this variant will adversely affect protein function
tolerated	moderately conservative	benign	benign
LRT	MutationTaster	MutationAssessor	FATHMM
deleterious	polymorphism (auto)	low impact	tolerated

References

1. Roddy Walsh, Kate L. Thomson, James S. Ware, Birgit H. Funke, Jessica Woodley, Karen J. McGuire, Francesco Mazzarotto, Edward Blair, Anneke Seller, Jenny C. Taylor, Eric V. Minikel, Exome Aggregation Consortium, Daniel G. MacArthur, Martin Farrall, Stuart A. Cook and Hugh Watkins. Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med. 2016 doi:10.1038/gim.2016.90.

2. Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med. 2014 Aug;16(8):601-8.

3. Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, McLaughlin HM, Clark EH, Babb LJ, Cox SW, DePalma SR, Ho CY, Seidman JG, Seidman CE, Rehm HL. Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genet Med. 2015 Nov;17(11):880-8.