Variant 22-31440758-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_019843.4(EIF4ENIF1):c.2662C>T(p.Arg888Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,613,904 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

EIF4ENIF1
NM_019843.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.64

Variant links:

Genes affected

EIF4ENIF1 (HGNC:16687): (eukaryotic translation initiation factor 4E nuclear import factor 1) The protein encoded by this gene is a nucleocytoplasmic shuttle protein for the translation initiation factor eIF4E. This shuttle protein interacts with the importin alpha-beta complex to mediate nuclear import of eIF4E. It is predominantly cytoplasmic; its own nuclear import is regulated by a nuclear localization signal and nuclear export signals. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

EIF4ENIF1 links:

EIF4ENIF1 (HGNC:):

EIF4ENIF1 links:

DRG1 (HGNC:3029): (developmentally regulated GTP binding protein 1) Enables several functions, including GTPase activity; identical protein binding activity; and potassium ion binding activity. Involved in positive regulation of microtubule polymerization and regulation of mitotic spindle assembly. Located in cytosol and nuclear body. Part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

DRG1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF4ENIF1	NM_019843.4 linkuse as main transcript	c.2662C>T	p.Arg888Cys	missense_variant	18/19	ENST00000330125.10	NP_062817.2	Q9NRA8-1A0A024R1K0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EIF4ENIF1	ENST00000330125.10 linkuse as main transcript	c.2662C>T	p.Arg888Cys	missense_variant	18/19	1	NM_019843.4	ENSP00000328103.5		Q9NRA8-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152222

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

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251192

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461682

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.2662C>T (p.R888C) alteration is located in exon 18 (coding exon 17) of the EIF4ENIF1 gene. This alteration results from a C to T substitution at nucleotide position 2662, causing the arginine (R) at amino acid position 888 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.33

.;T;T;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.96

D;.;D;D

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.55

D;D;D;D

MetaSVM

Uncertain

-0.20

MutationAssessor

Uncertain

2.3

.;M;M;.

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.9

D;N;N;D

REVEL

Benign

0.18

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Uncertain

0.013

D;D;D;D

Polyphen

1.0, 0.0020

.;D;D;B

Vest4

0.74

MutPred

0.29

.;Gain of catalytic residue at P887 (P = 0.0467);Gain of catalytic residue at P887 (P = 0.0467);.;

MVP

0.39

MPC

0.74

ClinPred

0.91

GERP RS

4.9

Varity_R

0.38

gMVP

0.61

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