Variant 11-7987468-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003754.3(EIF3F):c.116C>T(p.Pro39Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 1,605,270 control chromosomes in the GnomAD database, including 700 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.038 ( 148 hom., cov: 33)

Exomes 𝑓: 0.025 ( 552 hom. )

Consequence

EIF3F
NM_003754.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.78

Variant links:

Genes affected

EIF3F (HGNC:3275): (eukaryotic translation initiation factor 3 subunit F) Enables deubiquitinase activity and identical protein binding activity. Contributes to translation initiation factor activity. Involved in IRES-dependent viral translational initiation; protein deubiquitination; and translational initiation. Located in membrane. Part of eukaryotic translation initiation factor 3 complex. Implicated in autosomal recessive non-syndromic intellectual disability. [provided by Alliance of Genome Resources, Apr 2022]

EIF3F links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002229333).

BP6

Variant 11-7987468-C-T is Benign according to our data. Variant chr11-7987468-C-T is described in ClinVar as [Benign]. Clinvar id is 3056649.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF3F	NM_003754.3 linkuse as main transcript	c.116C>T	p.Pro39Leu	missense_variant	1/8	ENST00000651655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF3F	ENST00000651655.1 linkuse as main transcript	c.116C>T	p.Pro39Leu	missense_variant	1/8		NM_003754.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0382

AC:

5808

AN:

152192

Hom.:

147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0746

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0252

Gnomad ASJ

AF:

0.0204

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0388

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0253

Gnomad OTH

AF:

0.0383

GnomAD3 exomes

AF:

0.0230

AC:

5353

AN:

232710

Hom.:

105

AF XY:

0.0215

AC XY:

2763

AN XY:

128382

show subpopulations

Gnomad AFR exome

AF:

0.0755

Gnomad AMR exome

AF:

0.0136

Gnomad ASJ exome

AF:

0.0256

Gnomad EAS exome

AF:

0.0000570

Gnomad SAS exome

AF:

0.00419

Gnomad FIN exome

AF:

0.0388

Gnomad NFE exome

AF:

0.0255

Gnomad OTH exome

AF:

0.0232

GnomAD4 exome

AF:

0.0247

AC:

35855

AN:

1452960

Hom.:

552

Cov.:

AF XY:

0.0240

AC XY:

17326

AN XY:

722892

show subpopulations

Gnomad4 AFR exome

AF:

0.0748

Gnomad4 AMR exome

AF:

0.0156

Gnomad4 ASJ exome

AF:

0.0243

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00444

Gnomad4 FIN exome

AF:

0.0370

Gnomad4 NFE exome

AF:

0.0255

Gnomad4 OTH exome

AF:

0.0240

GnomAD4 genome

AF:

0.0382

AC:

5817

AN:

152310

Hom.:

148

Cov.:

AF XY:

0.0377

AC XY:

2805

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0746

Gnomad4 AMR

AF:

0.0251

Gnomad4 ASJ

AF:

0.0204

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0388

Gnomad4 NFE

AF:

0.0253

Gnomad4 OTH

AF:

0.0379

Alfa

AF:

0.0284

Hom.:

Bravo

AF:

0.0393

TwinsUK

AF:

0.0232

AC:

ALSPAC

AF:

0.0236

AC:

ExAC

AF:

0.0227

AC:

2649

Asia WGS

AF:

0.00636

AC:

AN:

3476

EpiCase

AF:

0.0245

EpiControl

AF:

0.0256

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

EIF3F-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.0077

T;T;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.086

MetaRNN

Benign

0.0022

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.69

N;N;.

REVEL

Benign

0.040

Sift

Benign

0.51

T;T;.

Sift4G

Benign

0.16

T;T;.

Polyphen

0.21

B;B;.

Vest4

0.097

MPC

0.28

ClinPred

0.0063

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.31

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over