chr3-184320988-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_198241.3(EIF4G1):āc.692G>Cā(p.Arg231Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,748 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 (no stars).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
EIF4G1
NM_198241.3 missense
NM_198241.3 missense
Scores
2
7
10
Clinical Significance
Conservation
PhyloP100: 4.86
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26895744).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250780Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135654
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461542Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727076
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74362
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
EIF4G1-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 23, 2024 | The EIF4G1 c.692G>C variant is predicted to result in the amino acid substitution p.Arg231Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0046% of alleles in individuals of European (Finnish) descent in gnomAD. 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
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;T;.;T;.;T;.;T;.;.;.;T;.;.;.;T;T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;.;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;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.;.;.;.;.;.;.;L;.;.;.;.;.;.;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;D;N;N;N;N;N;N;N;N;N;N;N;D;N;D;D;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4
MutPred
Gain of catalytic residue at R231 (P = 0.0045);.;.;.;.;Gain of catalytic residue at R231 (P = 0.0045);.;.;.;.;.;Gain of catalytic residue at R231 (P = 0.0045);.;.;.;.;.;.;.;.;.;
MVP
MPC
2.0
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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gMVP
Splicing
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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