Genetic Variant EIF3F:p.Pro78Leu (chr11-7987585-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003754.3(EIF3F):c.233C>T(p.Pro78Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,597,554 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 6 hom. )

Consequence

EIF3F
NM_003754.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.320

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059174597).

BP6

Variant 11-7987585-C-T is Benign according to our data. Variant chr11-7987585-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2578652.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EIF3F	NM_003754.3 link	c.233C>T	p.Pro78Leu	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.233C>T	p.Pro78Leu	missense_variant	Exon 1 of 8		NM_003754.3	ENSP00000499218.1		O00303

Frequencies

GnomAD3 genomes

AF:

0.00107

AC:

163

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00125

AC:

285

AN:

227346

Hom.:

AF XY:

0.00134

AC XY:

167

AN XY:

124880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00761

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000909

Gnomad FIN exome

AF:

0.0000491

Gnomad NFE exome

AF:

0.00161

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00128

AC:

1852

AN:

1445174

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

956

AN XY:

717398

show subpopulations

Gnomad4 AFR exome

AF:

0.000275

Gnomad4 AMR exome

AF:

0.000673

Gnomad4 ASJ exome

AF:

0.00807

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000925

Gnomad4 FIN exome

AF:

0.000152

Gnomad4 NFE exome

AF:

0.00126

Gnomad4 OTH exome

AF:

0.00185

GnomAD4 genome

AF:

0.00107

AC:

163

AN:

152380

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00138

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00221

Hom.:

Bravo

AF:

0.00133

ESP6500AA

AF:

0.000249

AC:

ESP6500EA

AF:

0.00123

AC:

ExAC

AF:

0.00122

AC:

147

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

EIF3F-related disorder

Benign:1

May 10, 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). -

not provided

Benign:1

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EIF3F: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0086

T;T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.050

M_CAP

Benign

0.021

MetaRNN

Benign

0.0059

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L;.

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.62

N;N;.

REVEL

Benign

0.083

Sift

Uncertain

0.0050

D;D;.

Sift4G

Uncertain

0.034

D;D;.

Polyphen

0.0020

B;B;.

Vest4

0.14

MVP

0.13

MPC

0.28

ClinPred

0.057

GERP RS

3.0

Varity_R

0.080

gMVP

0.20

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