1-20807390-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001391906.1(EIF4G3):c.4855G>A(p.Val1619Met) variant causes a missense change. The variant allele was found at a frequency of 0.000061 in 1,459,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000061 ( 0 hom. )
Consequence
EIF4G3
NM_001391906.1 missense
NM_001391906.1 missense
Scores
6
9
2
Clinical Significance
Conservation
PhyloP100: 6.15
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, EIF4G3
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EIF4G3 | NM_001391906.1 | c.4855G>A | p.Val1619Met | missense_variant | 37/37 | ENST00000602326.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EIF4G3 | ENST00000602326.6 | c.4855G>A | p.Val1619Met | missense_variant | 37/37 | 1 | NM_001391906.1 | A2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250542Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135400
GnomAD3 exomes
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GnomAD4 exome AF: 0.0000610 AC: 89AN: 1459866Hom.: 0 Cov.: 30 AF XY: 0.0000675 AC XY: 49AN XY: 726234
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
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Bravo
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ESP6500AA
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0
ESP6500EA
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1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 06, 2022 | The c.4795G>A (p.V1599M) alteration is located in exon 35 (coding exon 31) of the EIF4G3 gene. This alteration results from a G to A substitution at nucleotide position 4795, causing the valine (V) at amino acid position 1599 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;.;.
REVEL
Pathogenic
Sift
Uncertain
D;D;.;.;.
Sift4G
Uncertain
D;D;D;D;D
Polyphen
0.39
.;B;.;.;.
Vest4
MVP
MPC
1.1
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at