Variant 12-10506741-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001357734.3(EIF2S3B):c.839G>A(p.Gly280Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00546 in 1,614,002 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 28 hom. )

Consequence

EIF2S3B
NM_001357734.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.01

Variant links:

Genes affected

EIF2S3B (HGNC:43863): (eukaryotic translation initiation factor 2 subunit gamma B) Predicted to enable translation initiation factor activity. Predicted to contribute to tRNA binding activity. Predicted to be involved in formation of translation preinitiation complex and positive regulation of translational fidelity. Predicted to be part of eukaryotic translation initiation factor 2 complex. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

EIF2S3B links:

LOC105369657 (HGNC:):

LOC105369657 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=0.061276555).

BP6

Variant 12-10506741-G-A is Benign according to our data. Variant chr12-10506741-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642701.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EIF2S3B	NM_001357734.3 linkuse as main transcript	c.839G>A	p.Gly280Asp	missense_variant	1/1	ENST00000538173.2
LOC105369657	XR_931355.4 linkuse as main transcript	n.443-6140C>T		intron_variant, non_coding_transcript_variant
EIF2S3B	NM_001357731.1 linkuse as main transcript	c.839G>A	p.Gly280Asp	missense_variant	1/2
LOC105369657	XR_001749003.3 linkuse as main transcript	n.443-6140C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EIF2S3B	ENST00000538173.2 linkuse as main transcript	c.839G>A	p.Gly280Asp	missense_variant	1/1		NM_001357734.3	P1	Q2VIR3-1
EIF2S3B	ENST00000322446.3 linkuse as main transcript	c.839G>A	p.Gly280Asp	missense_variant	1/2	1			Q2VIR3-2

Frequencies

GnomAD3 genomes

AF:

0.00346

AC:

526

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00594

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00341

AC:

857

AN:

251466

Hom.:

AF XY:

0.00348

AC XY:

473

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00282

Gnomad NFE exome

AF:

0.00626

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00567

AC:

8293

AN:

1461716

Hom.:

Cov.:

AF XY:

0.00549

AC XY:

3993

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.000806

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00331

Gnomad4 NFE exome

AF:

0.00698

Gnomad4 OTH exome

AF:

0.00417

GnomAD4 genome

AF:

0.00345

AC:

526

AN:

152286

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

218

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00189

Gnomad4 NFE

AF:

0.00594

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00115

Hom.:

Bravo

AF:

0.00362

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00467

AC:

ExAC

AF:

0.00329

AC:

399

EpiCase

AF:

0.00573

EpiControl

AF:

0.00569

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

EIF2S3B: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.36

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.0043

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-0.60

PROVEAN

Pathogenic

-6.8

D;D

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.75

MVP

0.55

MPC

0.50

ClinPred

0.11

GERP RS

0.37

Varity_R

0.82

gMVP

0.86

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