SEPN1 : c.425G>A

SEPN1 gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.425G>Ap.C142Y (Cys > Tyr)substitutionmissense chr1:26131654 (forward strand)0.81442752

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.81442752 (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
ExAC0.77770278
51851 / 66672		0.78038815
7640 / 9790		0.94157199
8122 / 8626		0.88045058
14538 / 16512		0.91499654
10592 / 11576		0.72815240
4816 / 6614		0.81584821
731 / 896		0.81442752
98290 / 120686
ESP 0.00000
0 / 8600		 0.00000
0 / 4400		 0.00000
0 / 13000
1KG
 0.77970
630 / 808		 0.74508
985 / 1322		 0.93948
947 / 1008		 0.89980
880 / 978		 0.89193
619 / 694		 0.78283
155 / 198		 0.84185
4216 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.75824
138 / 182
British
0.77869
95 / 122
African-American
0.98387
183 / 186
Chinese Dai
0.91860
158 / 172
Bengali
0.92021
173 / 188
Colombian
0.74766
160 / 214
Iberian
0.70312
135 / 192
African-Caribbean
0.91748
189 / 206
Han, Beijing
0.88350
182 / 206
Gujarati Indian
0.90625
116 / 128
Mexican, LA
0.84112
180 / 214
Toscani
0.76263
151 / 198
Esan, Nigeria
0.90865
189 / 208
Japanese
0.94118
192 / 204
Indian Telugu
0.93529
159 / 170
Peruvian
0.76768
152 / 198
Utah Europeans
0.75221
170 / 226
Gambian
0.96970
192 / 198
Kinh, Vietnam
0.88542
170 / 192
Punjabi, Lahore
0.82212
171 / 208
Puerto Rican
0.72222
143 / 198
Luhya, Kenya
0.92381
194 / 210
Southern Han
0.87255
178 / 204
Tamil
0.74706
127 / 170
Mende
0.75926
164 / 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 ENST00000361547 NM_020451.2
Protein ENSP00000355141 Q9NZV5

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 radical benign benign
LRT MutationTaster MutationAssessor FATHMM
neutral 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.