Variant rs35176330 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001391906.1(EIF4G3):c.1654C>G(p.Pro552Ala) variant causes a missense change. The variant allele was found at a frequency of 0.029 in 1,609,296 control chromosomes in the GnomAD database, including 803 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.025 ( 82 hom., cov: 32)

Exomes 𝑓: 0.029 ( 721 hom. )

Consequence

EIF4G3
NM_001391906.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.06

Variant links:

Genes affected

EIF4G3 (HGNC:3298): (eukaryotic translation initiation factor 4 gamma 3) The protein encoded by this gene is thought to be part of the eIF4F protein complex, which is involved in mRNA cap recognition and transport of mRNAs to the ribosome. Interestingly, a microRNA (miR-520c-3p) has been found that negatively regulates synthesis of the encoded protein, and this leads to a global decrease in protein translation and cell proliferation. Therefore, this protein is a key component of the anti-tumor activity of miR-520c-3p. [provided by RefSeq, May 2016]

EIF4G3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019055307).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0245 (3734/152258) while in subpopulation NFE AF= 0.0331 (2248/68006). AF 95% confidence interval is 0.0319. There are 82 homozygotes in gnomad4. There are 1937 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 82 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4G3	NM_001391906.1 linkuse as main transcript	c.1654C>G	p.Pro552Ala	missense_variant	14/37	ENST00000602326.6	NP_001378835.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4G3	ENST00000602326.6 linkuse as main transcript	c.1654C>G	p.Pro552Ala	missense_variant	14/37	1	NM_001391906.1	ENSP00000473510	A2

Frequencies

GnomAD3 genomes

AF:

0.0245

AC:

3734

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00536

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0212

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0155

Gnomad FIN

AF:

0.0662

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0331

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.0274

AC:

6766

AN:

246638

Hom.:

147

AF XY:

0.0289

AC XY:

3852

AN XY:

133264

show subpopulations

Gnomad AFR exome

AF:

0.00536

Gnomad AMR exome

AF:

0.0127

Gnomad ASJ exome

AF:

0.0301

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0144

Gnomad FIN exome

AF:

0.0615

Gnomad NFE exome

AF:

0.0362

Gnomad OTH exome

AF:

0.0310

GnomAD4 exome

AF:

0.0294

AC:

42905

AN:

1457038

Hom.:

721

Cov.:

AF XY:

0.0294

AC XY:

21273

AN XY:

724624

show subpopulations

Gnomad4 AFR exome

AF:

0.00451

Gnomad4 AMR exome

AF:

0.0136

Gnomad4 ASJ exome

AF:

0.0326

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0151

Gnomad4 FIN exome

AF:

0.0593

Gnomad4 NFE exome

AF:

0.0316

Gnomad4 OTH exome

AF:

0.0275

GnomAD4 genome

AF:

0.0245

AC:

3734

AN:

152258

Hom.:

Cov.:

AF XY:

0.0260

AC XY:

1937

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00534

Gnomad4 AMR

AF:

0.0212

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0157

Gnomad4 FIN

AF:

0.0662

Gnomad4 NFE

AF:

0.0331

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.0297

Hom.:

Bravo

AF:

0.0207

TwinsUK

AF:

0.0280

AC:

104

ALSPAC

AF:

0.0291

AC:

112

ESP6500AA

AF:

0.00635

AC:

ESP6500EA

AF:

0.0320

AC:

275

ExAC

AF:

0.0277

AC:

3358

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.33

T;.;T;T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

0.013

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.97

D;D;D;D;D

MetaRNN

Benign

0.0019

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.5

D;.;.;.;.

REVEL

Benign

0.071

Sift

Uncertain

0.014

D;.;.;.;.

Sift4G

Uncertain

0.021

D;D;D;D;T

Polyphen

0.11

B;.;.;.;.

Vest4

0.21

MPC

0.17

ClinPred

0.033

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.073

gMVP

0.15

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over