Genetic Variant EIF3F:p.Pro12Leu (chr11-7987387-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003754.3(EIF3F):c.35C>T(p.Pro12Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0498 in 1,598,832 control chromosomes in the GnomAD database, including 3,079 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 (no stars).

Frequency

Genomes: 𝑓 0.044 ( 273 hom., cov: 33)

Exomes 𝑓: 0.050 ( 2806 hom. )

Consequence

EIF3F
NM_003754.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.09

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014544427).

BP6

Variant 11-7987387-C-T is Benign according to our data. Variant chr11-7987387-C-T is described in ClinVar as [Benign]. Clinvar id is 3060960.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3F	NM_003754.3 link	c.35C>T	p.Pro12Leu	missense_variant	Exon 1 of 8	ENST00000651655.1	NP_003745.1	O00303

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EIF3F	ENST00000651655.1 link	c.35C>T	p.Pro12Leu	missense_variant	Exon 1 of 8		NM_003754.3	ENSP00000499218.1		O00303

Frequencies

GnomAD3 genomes

AF:

0.0438

AC:

6663

AN:

152222

Hom.:

269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0105

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0190

Gnomad FIN

AF:

0.0963

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0467

Gnomad OTH

AF:

0.0406

GnomAD3 exomes

AF:

0.0648

AC:

14934

AN:

230556

Hom.:

1141

AF XY:

0.0569

AC XY:

7244

AN XY:

127306

show subpopulations

Gnomad AFR exome

AF:

0.00917

Gnomad AMR exome

AF:

0.223

Gnomad ASJ exome

AF:

0.0311

Gnomad EAS exome

AF:

0.000400

Gnomad SAS exome

AF:

0.0199

Gnomad FIN exome

AF:

0.0901

Gnomad NFE exome

AF:

0.0449

Gnomad OTH exome

AF:

0.0563

GnomAD4 exome

AF:

0.0504

AC:

72960

AN:

1446492

Hom.:

2806

Cov.:

AF XY:

0.0486

AC XY:

34998

AN XY:

719894

show subpopulations

Gnomad4 AFR exome

AF:

0.00803

Gnomad4 AMR exome

AF:

0.206

Gnomad4 ASJ exome

AF:

0.0289

Gnomad4 EAS exome

AF:

0.000505

Gnomad4 SAS exome

AF:

0.0216

Gnomad4 FIN exome

AF:

0.0895

Gnomad4 NFE exome

AF:

0.0492

Gnomad4 OTH exome

AF:

0.0419

GnomAD4 genome

AF:

0.0438

AC:

6674

AN:

152340

Hom.:

273

Cov.:

AF XY:

0.0468

AC XY:

3488

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0105

Gnomad4 AMR

AF:

0.112

Gnomad4 ASJ

AF:

0.0323

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0188

Gnomad4 FIN

AF:

0.0963

Gnomad4 NFE

AF:

0.0467

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0439

Hom.:

Bravo

AF:

0.0460

TwinsUK

AF:

0.0367

AC:

136

ALSPAC

AF:

0.0423

AC:

163

ESP6500AA

AF:

0.00877

AC:

ESP6500EA

AF:

0.0417

AC:

310

ExAC

AF:

0.0561

AC:

6626

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.0393

EpiControl

AF:

0.0410

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EIF3F-related disorder

Benign:1

Sep 26, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0090

T;T;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.16

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;L;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.78

N;N;.

REVEL

Benign

0.025

Sift

Benign

0.29

T;T;.

Sift4G

Uncertain

0.019

D;D;.

Polyphen

0.088

B;B;.

Vest4

0.33

MPC

0.28

ClinPred

0.039

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.036

gMVP

0.19

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