Genetic Variant EIF3E:p.Arg111Lys (chr8-108236195-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001568.3(EIF3E):c.332G>A(p.Arg111Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

EIF3E
NM_001568.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.81

Publications

0 publications found

Variant links:

Genes affected

EIF3E (HGNC:3277): (eukaryotic translation initiation factor 3 subunit E) Enables protein N-terminus binding activity. Contributes to translation initiation factor activity. Involved in positive regulation of mRNA binding activity; regulation of gene expression; and translational initiation. Located in cytosol and nucleus. Part of eukaryotic translation initiation factor 3 complex. Colocalizes with PML body. [provided by Alliance of Genome Resources, Apr 2022]

EIF3E links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32935807).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001568.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3E	NM_001568.3	MANE Select	c.332G>A	p.Arg111Lys	missense	Exon 4 of 13	NP_001559.1	P60228

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF3E	ENST00000220849.10	TSL:1 MANE Select	c.332G>A	p.Arg111Lys	missense	Exon 4 of 13	ENSP00000220849.5	P60228
EIF3E	ENST00000518442.5	TSL:1	c.332G>A	p.Arg111Lys	missense	Exon 4 of 5	ENSP00000504091.1	A0A7I2V570
EIF3E	ENST00000521440.6	TSL:1	c.185G>A	p.Arg62Lys	missense	Exon 5 of 7	ENSP00000430152.2	H0YBR5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74304

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000241

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5208

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Uncertain

0.068

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.071

Eigen

Benign

-0.17

Eigen_PC

Benign

0.080

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.019

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.42

PhyloP100

5.8

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.11

REVEL

Benign

0.17

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.48

MutPred

0.41

Gain of ubiquitination at R111 (P = 0.009)

MVP

0.72

MPC

0.91

ClinPred

0.94

GERP RS

5.3

Varity_R

0.22

gMVP

0.47

Mutation Taster

=41/59

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over