TMEM43 : c.504A>T

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.504A>T	p.K168N (Lys > Asn)	substitution	missense	chr3:14174427 (forward strand)	0.32086637

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.32086637 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

DCM	OMGL: Detected in 0 / 304 DCM patients. LMM: Detected in 0 / 123 DCM patients.
ARVC	OMGL: Detected in 0 / 94 ARVC patients sequenced at OMGL.

DCM

OMGL: Detected in 0 / 304 DCM patients.

LMM: Detected in 0 / 123 DCM patients.

ARVC

OMGL: Detected in 0 / 94 ARVC patients sequenced at OMGL.

For more information on the clinical significance of this variant, please see the ClinVar entry.

Detection in Population Databases

Database	European	African	East Asian	South Asian	American	Finnish	Other	Total
ExAC	0.27924025 18627 / 66706	0.28613995 2977 / 10404	0.43664582 3770 / 8634	0.37278895 6154 / 16508	0.44087137 5100 / 11568	0.30039346 1985 / 6608	0.35209713 319 / 906	0.32086637 38932 / 121334
ESP	0.28779 2475 / 8600	0.28711 1265 / 4406						0.28756 3740 / 13006
1KG	0.25248 204 / 808	0.30257 400 / 1322	0.46131 465 / 1008	0.39980 391 / 978	0.36599 254 / 694	0.26263 52 / 198		0.35264 1766 / 5008

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

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

0.25824 47 / 182 British	0.31967 39 / 122 African-American	0.54301 101 / 186 Chinese Dai	0.44186 76 / 172 Bengali	0.34574 65 / 188 Colombian
0.25234 54 / 214 Iberian	0.31250 60 / 192 African-Caribbean	0.41748 86 / 206 Han, Beijing	0.34466 71 / 206 Gujarati Indian	0.39844 51 / 128 Mexican, LA
0.24766 53 / 214 Toscani	0.29798 59 / 198 Esan, Nigeria	0.38462 80 / 208 Japanese	0.45098 92 / 204 Indian Telugu	0.42353 72 / 170 Peruvian
0.25253 50 / 198 Utah Europeans	0.26991 61 / 226 Gambian	0.54545 108 / 198 Kinh, Vietnam	0.32812 63 / 192 Punjabi, Lahore	0.31731 66 / 208 Puerto Rican
	0.38889 77 / 198 Luhya, Kenya	0.42857 90 / 210 Southern Han	0.43627 89 / 204 Tamil
	0.24118 41 / 170 Mende
	0.29167 63 / 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	ENST00000306077	LRG_435t1	NM_024334.2
Protein	ENSP00000303992	LRG_435p1		Q9BTV4

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.