Genetic Variant NM_001134651.2:c.64G>T (chr3-71725304-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001134651.2(EIF4E3):c.64G>T(p.Ala22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000475 in 842,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A22T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

EIF4E3
NM_001134651.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.257

Publications

0 publications found

Variant links:

Genes affected

EIF4E3 (HGNC:31837): (eukaryotic translation initiation factor 4E family member 3) EIF4E3 belongs to the EIF4E family of translational initiation factors that interact with the 5-prime cap structure of mRNA and recruit mRNA to the ribosome (Joshi et al., 2004 [PubMed 15153109]).[supplied by OMIM, Mar 2008]

EIF4E3 links:

ENSG00000285708 (HGNC:):

ENSG00000285708 links:

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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 (MetaRNN=0.15464318).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134651.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF4E3	NM_001134651.2	MANE Select	c.64G>T	p.Ala22Ser	missense	Exon 1 of 7	NP_001128123.1	Q8N5X7-1
EIF4E3	NM_001134649.3		c.-143+3172G>T		intron	N/A	NP_001128121.1	Q8N5X7-2
EIF4E3	NM_001134650.1		c.-143+3172G>T		intron	N/A	NP_001128122.1	Q8N5X7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF4E3	ENST00000425534.8	TSL:2 MANE Select	c.64G>T	p.Ala22Ser	missense	Exon 1 of 7	ENSP00000393324.2	Q8N5X7-1
ENSG00000285708	ENST00000647725.1		c.-811+3172G>T		intron	N/A	ENSP00000497585.1
EIF4E3	ENST00000295612.7	TSL:1	c.-143+3172G>T		intron	N/A	ENSP00000295612.3	Q8N5X7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000475

AC:

AN:

842488

Hom.:

Cov.:

AF XY:

0.00000768

AC XY:

AN XY:

390860

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15884

American (AMR)

AF:

0.00

AC:

AN:

1506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5552

East Asian (EAS)

AF:

0.00

AC:

AN:

4298

South Asian (SAS)

AF:

0.00

AC:

AN:

17266

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2186

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1704

European-Non Finnish (NFE)

AF:

0.00000522

AC:

AN:

766104

Other (OTH)

AF:

0.00

AC:

AN:

27988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.2

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.024

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.33

M_CAP

Benign

0.037

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-0.26

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.46

REVEL

Benign

0.10

Sift

Benign

0.71

Sift4G

Benign

0.73

Polyphen

0.98

Vest4

0.13

MutPred

0.50

Loss of helix (P = 0.0104)

MVP

0.27

MPC

0.025

ClinPred

0.14

GERP RS

0.96

PromoterAI

-0.0027

Neutral

(source)

Varity_R

0.038

gMVP

0.32

Mutation Taster

=92/8

polymorphism

(source)

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

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