1-20829180-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001391906.1(EIF4G3):ā€‹c.4154A>Gā€‹(p.Lys1385Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

EIF4G3
NM_001391906.1 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.65
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16909969).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EIF4G3NM_001391906.1 linkc.4154A>G p.Lys1385Arg missense_variant Exon 31 of 37 ENST00000602326.6 NP_001378835.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EIF4G3ENST00000602326.6 linkc.4154A>G p.Lys1385Arg missense_variant Exon 31 of 37 1 NM_001391906.1 ENSP00000473510.2 A0A8J9G7U8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461704
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727148
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 27, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.4094A>G (p.K1365R) alteration is located in exon 29 (coding exon 25) of the EIF4G3 gene. This alteration results from a A to G substitution at nucleotide position 4094, causing the lysine (K) at amino acid position 1365 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.045
.;T;.;T;T
Eigen
Benign
-0.070
Eigen_PC
Benign
0.12
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.91
D;D;D;D;D
M_CAP
Benign
0.0056
T
MetaRNN
Benign
0.17
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.95
.;L;.;.;.
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.79
N;N;.;N;.
REVEL
Benign
0.068
Sift
Benign
0.34
T;T;.;T;.
Sift4G
Benign
0.84
T;T;T;T;T
Polyphen
0.17
.;B;.;.;.
Vest4
0.21
MutPred
0.41
.;Loss of ubiquitination at K1329 (P = 0.027);.;.;.;
MVP
0.45
MPC
0.87
ClinPred
0.87
D
GERP RS
5.7
Varity_R
0.23
gMVP
0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-21155673; API