GeneBe

rs1805190

Positions:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004836.7(EIF2AK3):​c.52_63del​(p.Leu18_Leu21del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000469 in 1,278,918 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

EIF2AK3
NM_004836.7 inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.66
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EIF2AK3NM_004836.7 linkuse as main transcriptc.52_63del p.Leu18_Leu21del inframe_deletion 1/17 ENST00000303236.9 NP_004827.4
EIF2AK3XM_047446430.1 linkuse as main transcriptc.52_63del p.Leu18_Leu21del inframe_deletion 1/12 XP_047302386.1
EIF2AK3XM_047446428.1 linkuse as main transcriptc.17+466_17+477del intron_variant XP_047302384.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EIF2AK3ENST00000303236.9 linkuse as main transcriptc.52_63del p.Leu18_Leu21del inframe_deletion 1/171 NM_004836.7 ENSP00000307235 P1
EIF2AK3ENST00000682892.1 linkuse as main transcriptc.-145-13370_-145-13359del intron_variant ENSP00000507214
EIF2AK3ENST00000652099.1 linkuse as main transcriptc.50_61del p.Leu18_Leu21del inframe_deletion, NMD_transcript_variant 1/18 ENSP00000498211
EIF2AK3ENST00000652423.1 linkuse as main transcriptc.52_63del p.Leu18_Leu21del inframe_deletion, NMD_transcript_variant 1/4 ENSP00000498948

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD3 exomes
AF:
0.0000153
AC:
1
AN:
65220
Hom.:
0
AF XY:
0.0000268
AC XY:
1
AN XY:
37308
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000710
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000469
AC:
6
AN:
1278918
Hom.:
0
AF XY:
0.00000794
AC XY:
5
AN XY:
630064
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000284
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000392
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1805190; hg19: chr2-88926729; API