GeneBe

rs886056412

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004836.7(EIF2AK3):​c.*459G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

EIF2AK3
NM_004836.7 3_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.56

Publications

0 publications found
Variant links:
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 syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, G2P, Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.25).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004836.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
EIF2AK3
NM_004836.7
MANE Select
c.*459G>T
3_prime_UTR
Exon 17 of 17NP_004827.4
EIF2AK3
NM_001313915.2
c.*459G>T
3_prime_UTR
Exon 17 of 17NP_001300844.1A0A804HIT4
EIF2AK3-AS1
NR_110236.1
n.650+17098C>A
intron
N/A

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
EIF2AK3
ENST00000303236.9
TSL:1 MANE Select
c.*459G>T
3_prime_UTR
Exon 17 of 17ENSP00000307235.3Q9NZJ5
EIF2AK3-AS1
ENST00000413234.1
TSL:1
n.650+17098C>A
intron
N/A
EIF2AK3
ENST00000682892.1
c.*459G>T
3_prime_UTR
Exon 18 of 18ENSP00000507214.1A0A804HIT4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
26582
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
13656
African (AFR)
AF:
0.00
AC:
0
AN:
306
American (AMR)
AF:
0.00
AC:
0
AN:
3060
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
418
East Asian (EAS)
AF:
0.00
AC:
0
AN:
1744
South Asian (SAS)
AF:
0.00
AC:
0
AN:
3156
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
1366
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
70
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
15146
Other (OTH)
AF:
0.00
AC:
0
AN:
1316
GnomAD4 genome
Cov.:
32

ClinVar

ClinVar submissions as Germline
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
Wolcott-Rallison dysplasia (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.25
CADD
Benign
14
DANN
Benign
0.83
PhyloP100
1.6

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs886056412; hg19: chr2-88856795; API