Genetic Variant NM_001134651.2:c.89C>A (chr3-71725279-G-T) – 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.89C>A(p.Pro30Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000393 in 1,017,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

EIF4E3
NM_001134651.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00600

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=0.12661815).

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.89C>A	p.Pro30Gln	missense	Exon 1 of 7	NP_001128123.1	Q8N5X7-1
EIF4E3	NM_001134649.3		c.-143+3197C>A		intron	N/A	NP_001128121.1	Q8N5X7-2
EIF4E3	NM_001134650.1		c.-143+3197C>A		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.89C>A	p.Pro30Gln	missense	Exon 1 of 7	ENSP00000393324.2	Q8N5X7-1
ENSG00000285708	ENST00000647725.1		c.-811+3197C>A		intron	N/A	ENSP00000497585.1
EIF4E3	ENST00000295612.7	TSL:1	c.-143+3197C>A		intron	N/A	ENSP00000295612.3	Q8N5X7-2

Frequencies

GnomAD3 genomes

AF:

0.0000136

AC:

AN:

147004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000302

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000230

AC:

AN:

870566

Hom.:

Cov.:

AF XY:

0.00000246

AC XY:

AN XY:

406086

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16540

American (AMR)

AF:

0.00

AC:

AN:

2076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6220

East Asian (EAS)

AF:

0.00

AC:

AN:

5742

South Asian (SAS)

AF:

0.00

AC:

AN:

17776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4224

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1838

European-Non Finnish (NFE)

AF:

0.00000254

AC:

AN:

786684

Other (OTH)

AF:

0.00

AC:

AN:

29466

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

AF:

0.0000136

AC:

AN:

147004

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71536

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40880

American (AMR)

AF:

0.00

AC:

AN:

14816

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3392

East Asian (EAS)

AF:

0.00

AC:

AN:

5108

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.0000302

AC:

AN:

66116

Other (OTH)

AF:

0.00

AC:

AN:

2028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.0000113

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

0.088

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.024

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.31

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.0060

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.050

REVEL

Benign

0.024

Sift

Benign

0.063

Sift4G

Benign

0.15

Polyphen

0.41

Vest4

0.097

MutPred

0.37

Loss of glycosylation at P31 (P = 0.0069)

MVP

0.25

MPC

0.025

ClinPred

0.19

GERP RS

0.66

PromoterAI

-0.044

Neutral

(source)

Varity_R

0.043

gMVP

0.29

Mutation Taster

=96/4

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over