WNK1 : c.3166A>C

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.3166A>C	p.T1056P (Thr > Pro)	substitution	missense	chr12:990912 (forward strand)	0.83141680

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.83141680 (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	0.83482183 55711 / 66734	0.86238708 8974 / 10406	0.79780347 6901 / 8650	0.83278828 13751 / 16512	0.86031444 9959 / 11576	0.74584215 4933 / 6614	0.77643172 705 / 908	0.83141680 100934 / 121400
ESP	0.85128 7321 / 8600	0.85520 3768 / 4406						0.85261 11089 / 13006
1KG	0.84653 684 / 808	0.86309 1141 / 1322	0.81746 824 / 1008	0.87526 856 / 978	0.87320 606 / 694	0.80808 160 / 198		0.85284 4271 / 5008

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

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

0.84066 153 / 182 British	0.85246 104 / 122 African-American	0.81720 152 / 186 Chinese Dai	0.88372 152 / 172 Bengali	0.88830 167 / 188 Colombian
0.82710 177 / 214 Iberian	0.88542 170 / 192 African-Caribbean	0.80097 165 / 206 Han, Beijing	0.88350 182 / 206 Gujarati Indian	0.88281 113 / 128 Mexican, LA
0.82243 176 / 214 Toscani	0.84848 168 / 198 Esan, Nigeria	0.83173 173 / 208 Japanese	0.87255 178 / 204 Indian Telugu	0.89412 152 / 170 Peruvian
0.89899 178 / 198 Utah Europeans	0.88053 199 / 226 Gambian	0.82828 164 / 198 Kinh, Vietnam	0.84896 163 / 192 Punjabi, Lahore	0.83654 174 / 208 Puerto Rican
	0.83333 165 / 198 Luhya, Kenya	0.80952 170 / 210 Southern Han	0.88725 181 / 204 Tamil
	0.84118 143 / 170 Mende
	0.88889 192 / 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 0% of algorithms have predicted that this variant will adversely affect protein function
tolerated	conservative	benign	benign
LRT	MutationTaster	MutationAssessor	FATHMM
neutral	polymorphism (auto)	neutral	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.