Variant 3-184319748-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_198241.3(EIF4G1):c.484C>A(p.Pro162Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EIF4G1
NM_198241.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.82

Variant links:

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]

EIF4G1 links:

EIF4G1 (HGNC:):

EIF4G1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), EIF4G1. . Gene score misZ 2.2233 (greater than the threshold 3.09). Trascript score misZ 4.0613 (greater than threshold 3.09). GenCC has associacion of gene with Parkinson disease 18, autosomal dominant, susceptibility to.

BP4

Computational evidence support a benign effect (MetaRNN=0.28615195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4G1	NM_198241.3 linkuse as main transcript	c.484C>A	p.Pro162Thr	missense_variant	7/33	ENST00000346169.7	NP_937884.2	Q04637-1Q96I65

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4G1	ENST00000346169.7 linkuse as main transcript	c.484C>A	p.Pro162Thr	missense_variant	7/33	1	NM_198241.3	ENSP00000316879.5		Q04637-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1456328

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723744

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.:

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

Aug 20, 2024

The c.505C>A (p.P169T) alteration is located in exon 8 (coding exon 6) of the EIF4G1 gene. This alteration results from a C to A substitution at nucleotide position 505, causing the proline (P) at amino acid position 169 to be replaced by a threonine (T). 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

0.066

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.;.;.;.;T;.;T;.;T;.;.;T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.88

D;D;D;D;D;D;.;D;D;D;D;.;D;D

M_CAP

Benign

0.0074

MetaRNN

Benign

0.29

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.;.;.;.;.;.;.;.;.;M;.;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.1

D;D;D;D;D;D;D;D;.;D;D;D;D;D

REVEL

Benign

0.025

Sift

Uncertain

0.029

D;D;D;D;D;D;D;D;.;D;D;D;D;D

Sift4G

Uncertain

0.026

D;D;D;D;D;D;D;D;T;D;D;D;T;D

Polyphen

0.52

P;.;.;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.14

MutPred

0.30

Gain of catalytic residue at P162 (P = 0.0283);.;.;.;Gain of catalytic residue at P162 (P = 0.0283);.;.;.;.;.;Gain of catalytic residue at P162 (P = 0.0283);.;.;.;

MVP

0.27

MPC

0.85

ClinPred

0.59

GERP RS

3.8

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.8

Varity_R

0.14

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over