Genetic Variant EIF4G3:p.Pro1466Leu (chr1-20817510-G-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_001391906.1(EIF4G3):c.4397C>T(p.Pro1466Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1466R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EIF4G3
NM_001391906.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.97

Publications

0 publications found

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:

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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=0.14429891).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001391906.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF4G3	NM_001391906.1	MANE Select	c.4397C>T	p.Pro1466Leu	missense	Exon 34 of 37	NP_001378835.1	A0A8J9G7U8
EIF4G3	NM_001391907.1		c.4487C>T	p.Pro1496Leu	missense	Exon 34 of 37	NP_001378836.1
EIF4G3	NM_001438678.1		c.4376C>T	p.Pro1459Leu	missense	Exon 33 of 36	NP_001425607.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF4G3	ENST00000602326.6	TSL:1 MANE Select	c.4397C>T	p.Pro1466Leu	missense	Exon 34 of 37	ENSP00000473510.2	A0A8J9G7U8
EIF4G3	ENST00000400422.6	TSL:1	c.4337C>T	p.Pro1446Leu	missense	Exon 32 of 35	ENSP00000383274.2	A0A0A0MSA7
EIF4G3	ENST00000693470.1		c.5159C>T	p.Pro1720Leu	missense	Exon 30 of 33	ENSP00000509295.1	A0A8I5KV92

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1452262

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722428

African (AFR)

AF:

0.00

AC:

AN:

33332

American (AMR)

AF:

0.00

AC:

AN:

44552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25860

East Asian (EAS)

AF:

0.00

AC:

AN:

39382

South Asian (SAS)

AF:

0.00

AC:

AN:

84604

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52698

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106240

Other (OTH)

AF:

0.00

AC:

AN:

59872

GnomAD4 genome

Cov.:

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

0.077

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

Eigen

Benign

0.0064

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.0091

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.4

PhyloP100

9.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.4

REVEL

Benign

0.083

Sift

Benign

0.038

Sift4G

Benign

0.13

Polyphen

0.0

Vest4

0.32

MutPred

0.22

Gain of helix (P = 0.062)

MVP

0.17

MPC

0.66

ClinPred

0.91

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.049

gMVP

0.36

Mutation Taster

=60/40

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over