NM_004836.7:c.*870_*875delATGTTT
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS1_Supporting
The NM_004836.7(EIF2AK3):c.*870_*875delATGTTT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.000138 in 152,366 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Consequence
EIF2AK3
NM_004836.7 3_prime_UTR
NM_004836.7 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.79
Publications
0 publications found
Genes affected
EIF2AK3 (HGNC:3255): (eukaryotic translation initiation factor 2 alpha kinase 3) The protein encoded by this gene phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2, leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. This protein is thought to modulate mitochondrial function. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Mutations in this gene are associated with Wolcott-Rallison syndrome. [provided by RefSeq, Sep 2015]
EIF2AK3 Gene-Disease associations (from GenCC):
- Wolcott-Rallison syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Genomics England PanelApp, G2P
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -1 ACMG points.
BS1
Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000138 (21/152366) while in subpopulation SAS AF = 0.00414 (20/4832). AF 95% confidence interval is 0.00274. There are 0 homozygotes in GnomAd4. There are 12 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.000138 AC: 21AN: 152248Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
21
AN:
152248
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.000138 AC: 21AN: 152366Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74512 show subpopulations
GnomAD4 genome
AF:
AC:
21
AN:
152366
Hom.:
Cov.:
32
AF XY:
AC XY:
12
AN XY:
74512
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41590
American (AMR)
AF:
AC:
1
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5190
South Asian (SAS)
AF:
AC:
20
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68038
Other (OTH)
AF:
AC:
0
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Wolcott-Rallison dysplasia Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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