rs1043738

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. P39P) has been classified as Likely benign.

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 no assertion criteria provided B:1

Conservation

PhyloP100: 1.78

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

syndromic intellectual disability
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
intellectual developmental disorder, autosomal recessive 67
Inheritance: AR, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

EIF3F links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 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 VariationId is 3056649.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003754.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3F	NM_003754.3	MANE Select	c.116C>T	p.Pro39Leu	missense	Exon 1 of 8	NP_003745.1	O00303

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EIF3F	ENST00000651655.1	MANE Select	c.116C>T	p.Pro39Leu	missense	Exon 1 of 8	ENSP00000499218.1	O00303
EIF3F	ENST00000531572.2	TSL:2	c.116C>T	p.Pro39Leu	missense	Exon 1 of 7	ENSP00000434286.2	H0YDT6
EIF3F	ENST00000533626.5	TSL:2	c.116C>T	p.Pro39Leu	missense	Exon 3 of 10	ENSP00000431800.1	O00303

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

GnomAD2 exomes

AF:

0.0230

AC:

5353

AN:

232710

AF XY:

0.0215

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 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

African (AFR)

AF:

0.0748

AC:

2493

AN:

33338

American (AMR)

AF:

0.0156

AC:

695

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.0243

AC:

631

AN:

26020

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39612

South Asian (SAS)

AF:

0.00444

AC:

382

AN:

85988

European-Finnish (FIN)

AF:

0.0370

AC:

1756

AN:

47440

Middle Eastern (MID)

AF:

0.0206

AC:

102

AN:

4960

European-Non Finnish (NFE)

AF:

0.0255

AC:

28349

AN:

1110868

Other (OTH)

AF:

0.0240

AC:

1446

AN:

60142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

2648

5296

7943

10591

13239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1078

2156

3234

4312

5390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0382

AC:

5817

AN:

152310

Hom.:

148

Cov.:

AF XY:

0.0377

AC XY:

2805

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0746

AC:

3102

AN:

41564

American (AMR)

AF:

0.0251

AC:

385

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0204

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00269

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0388

AC:

412

AN:

10616

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0253

AC:

1720

AN:

68022

Other (OTH)

AF:

0.0379

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

285

569

854

1138

1423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0227

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

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

EIF3F-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0077

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.086

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

1.8

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.69

REVEL

Benign

0.040

Sift

Benign

0.51

Sift4G

Benign

0.16

Polyphen

0.21

Vest4

0.097

MPC

0.28

ClinPred

0.0063

GERP RS

2.0

PromoterAI

0.079

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.31

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over