chr3-184319739-G-T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_198241.3(EIF4G1):c.475G>T(p.Ala159Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,607,242 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 (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
EIF4G1
NM_198241.3 missense
NM_198241.3 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 4.56
Genes affected
EIF4G1 (HGNC:3296): (eukaryotic translation initiation factor 4 gamma 1) The protein encoded by this gene is a component of the multi-subunit protein complex EIF4F. This complex facilitates the recruitment of mRNA to the ribosome, which is a rate-limiting step during the initiation phase of protein synthesis. The recognition of the mRNA cap and the ATP-dependent unwinding of 5'-terminal secondary structure is catalyzed by factors in this complex. The subunit encoded by this gene is a large scaffolding protein that contains binding sites for other members of the EIF4F complex. A domain at its N-terminus can also interact with the poly(A)-binding protein, which may mediate the circularization of mRNA during translation. Alternative splicing results in multiple transcript variants, some of which are derived from alternative promoter usage. [provided by RefSeq, Aug 2010]
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=0.24322364).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 30
GnomAD3 genomes
AF:
AC:
1
AN:
152154
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000421 AC: 1AN: 237744Hom.: 0 AF XY: 0.00000777 AC XY: 1AN XY: 128704
GnomAD3 exomes
AF:
AC:
1
AN:
237744
Hom.:
AF XY:
AC XY:
1
AN XY:
128704
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1455088Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 723042
GnomAD4 exome
AF:
AC:
1
AN:
1455088
Hom.:
Cov.:
29
AF XY:
AC XY:
1
AN XY:
723042
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74320
GnomAD4 genome
AF:
AC:
1
AN:
152154
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
74320
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
EIF4G1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 17, 2023 | The EIF4G1 c.475G>T variant is predicted to result in the amino acid substitution p.Ala159Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0059% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-184037527-G-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.;T;.;T;.;T;.;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;.;D;D;D;D;.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.;.;.;.;.;.;L;.;.;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;.;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;D;D;T;T;.;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
D;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4
MutPred
Loss of glycosylation at T156 (P = 0.0591);.;.;.;Loss of glycosylation at T156 (P = 0.0591);.;.;.;.;.;Loss of glycosylation at T156 (P = 0.0591);.;.;.;
MVP
MPC
1.6
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at