NM_001391906.1:c.4388C>G

Variant summary

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

The NM_001391906.1(EIF4G3):ā€‹c.4388C>Gā€‹(p.Ser1463Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00001 in 1,600,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1463A) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000053 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

EIF4G3
NM_001391906.1 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12
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=0.16517764).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EIF4G3NM_001391906.1 linkc.4388C>G p.Ser1463Cys missense_variant Exon 34 of 37 ENST00000602326.6 NP_001378835.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EIF4G3ENST00000602326.6 linkc.4388C>G p.Ser1463Cys missense_variant Exon 34 of 37 1 NM_001391906.1 ENSP00000473510.2 A0A8J9G7U8

Frequencies

GnomAD3 genomes
AF:
0.0000528
AC:
8
AN:
151598
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000967
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.00
Gnomad OTH
AF:
0.000959
GnomAD3 exomes
AF:
0.00000805
AC:
2
AN:
248362
Hom.:
0
AF XY:
0.00000744
AC XY:
1
AN XY:
134464
show subpopulations
Gnomad AFR exome
AF:
0.0000622
Gnomad AMR exome
AF:
0.0000294
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000552
AC:
8
AN:
1448646
Hom.:
0
Cov.:
30
AF XY:
0.00000971
AC XY:
7
AN XY:
720610
show subpopulations
Gnomad4 AFR exome
AF:
0.000180
Gnomad4 AMR exome
AF:
0.0000453
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
AF:
0.0000528
AC:
8
AN:
151598
Hom.:
0
Cov.:
31
AF XY:
0.0000675
AC XY:
5
AN XY:
74058
show subpopulations
Gnomad4 AFR
AF:
0.0000967
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000959
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000170
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.4328C>G (p.S1443C) alteration is located in exon 32 (coding exon 28) of the EIF4G3 gene. This alteration results from a C to G substitution at nucleotide position 4328, causing the serine (S) at amino acid position 1443 to be replaced by a cysteine (C). 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
0.095
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.35
.;T;.;T;T
Eigen
Benign
0.080
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.97
D;D;D;D;D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.17
T;T;T;T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Benign
1.6
.;L;.;.;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Uncertain
-2.9
D;D;.;.;.
REVEL
Benign
0.063
Sift
Uncertain
0.0040
D;D;.;.;.
Sift4G
Uncertain
0.0060
D;D;D;D;D
Polyphen
0.81
.;P;.;.;.
Vest4
0.51
MVP
0.39
MPC
0.62
ClinPred
0.80
D
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.56

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.

Other links and lift over

dbSNP: rs777487330; hg19: chr1-21144012; API