NEXN : c.733G>A

NEXN gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.733G>Ap.G245R (Gly > Arg)substitutionmissense chr1:78392446 (forward strand)0.18458650

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.18458650 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

HCM

LMM:   Detected in 0 / 632 HCM patients.

DCM

LMM:   Detected in 0 / 156 DCM patients.

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
ExAC0.21420412
14251 / 66530		0.03660292
356 / 9726		0.39474907
3398 / 8608		0.07809466
1287 / 16480		0.14281998
1647 / 11532		0.17039613
1127 / 6614		0.17371938
156 / 898		0.18458650
22222 / 120388
ESP 0.20731
1690 / 8152		 0.04658
169 / 3628		 0.15781
1859 / 11780
1KG
 0.21163
171 / 808		 0.01059
14 / 1322		 0.37996
383 / 1008		 0.06646
65 / 978		 0.11671
81 / 694		 0.20707
41 / 198		 0.15076
755 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.18681
34 / 182
British
0.05738
7 / 122
African-American
0.36559
68 / 186
Chinese Dai
0.08721
15 / 172
Bengali
0.13830
26 / 188
Colombian
0.22430
48 / 214
Iberian
0.03125
6 / 192
African-Caribbean
0.40777
84 / 206
Han, Beijing
0.04854
10 / 206
Gujarati Indian
0.12500
16 / 128
Mexican, LA
0.22430
48 / 214
Toscani
0.00000
0 / 198
Esan, Nigeria
0.40865
85 / 208
Japanese
0.05392
11 / 204
Indian Telugu
0.05882
10 / 170
Peruvian
0.20707
41 / 198
Utah Europeans
0.00442
1 / 226
Gambian
0.32323
64 / 198
Kinh, Vietnam
0.07292
14 / 192
Punjabi, Lahore
0.13942
29 / 208
Puerto Rican
0.00000
0 / 198
Luhya, Kenya
0.39048
82 / 210
Southern Han
0.07353
15 / 204
Tamil
0.00000
0 / 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 ENST00000334785 LRG_442t1NM_144573.3
Protein ENSP00000333938 LRG_442p1Q0ZGT2

Missense Variant Predictions
SIFT Grantham Polyphen-DIV Polyphen-VAR Summary
62.5% of algorithms have predicted that this variant will adversely affect protein function
tolerated moderately radical probably damaging probably damaging
LRT MutationTaster MutationAssessor FATHMM
deleterious polymorphism (auto) medium 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.