NM_003754.3:c.10C>G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003754.3(EIF3F):c.10C>G(p.Pro4Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,593,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P4S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

EIF3F
NM_003754.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.928

Publications

1 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15880373).

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.10C>G	p.Pro4Ala	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.10C>G	p.Pro4Ala	missense	Exon 1 of 8	ENSP00000499218.1	O00303
EIF3F	ENST00000531572.2	TSL:2	c.10C>G	p.Pro4Ala	missense	Exon 1 of 7	ENSP00000434286.2	H0YDT6
EIF3F	ENST00000533626.5	TSL:2	c.10C>G	p.Pro4Ala	missense	Exon 3 of 10	ENSP00000431800.1	O00303

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000132

AC:

AN:

227284

AF XY:

0.0000239

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000582

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1441226

Hom.:

Cov.:

AF XY:

0.00000837

AC XY:

AN XY:

716764

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33144

American (AMR)

AF:

0.00

AC:

AN:

43856

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25872

East Asian (EAS)

AF:

0.00

AC:

AN:

39464

South Asian (SAS)

AF:

0.00

AC:

AN:

85762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39052

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1108356

Other (OTH)

AF:

0.00

AC:

AN:

59994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000131

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74386

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41468

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68052

Other (OTH)

AF:

0.00

AC:

AN:

2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000847

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.010

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.024

M_CAP

Benign

0.021

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.81

PhyloP100

0.93

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.66

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Benign

0.18

Polyphen

0.99

Vest4

0.30

MutPred

0.29

Loss of phosphorylation at T3 (P = 0.0606)

MVP

0.15

MPC

0.27

ClinPred

0.26

GERP RS

3.3

PromoterAI

0.053

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.093

gMVP

0.29

Mutation Taster

=80/20

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over