Genetic Variant NM_001357734.3:c.839G>A (chr12-10506741-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2642701.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001357734.3. 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
	EIF2S3B	NM_001357734.3	MANE Select	c.839G>A	p.Gly280Asp	missense	Exon 1 of 1	NP_001344663.1	Q2VIR3-1
	EIF2S3B	NM_001357731.1		c.839G>A	p.Gly280Asp	missense	Exon 1 of 2	NP_001344660.1	Q2VIR3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF2S3B	ENST00000538173.2	TSL:6 MANE Select	c.839G>A	p.Gly280Asp	missense	Exon 1 of 1	ENSP00000445077.1	Q2VIR3-1
	EIF2S3B	ENST00000322446.3	TSL:1	c.839G>A	p.Gly280Asp	missense	Exon 1 of 2	ENSP00000323063.3	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

GnomAD2 exomes

AF:

0.00341

AC:

857

AN:

251466

AF XY:

0.00348

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 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

African (AFR)

AF:

0.000806

AC:

AN:

33480

American (AMR)

AF:

0.00152

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00331

AC:

177

AN:

53420

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00698

AC:

7762

AN:

1111846

Other (OTH)

AF:

0.00417

AC:

252

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

533

1066

1600

2133

2666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.00345

AC:

526

AN:

152286

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

218

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00116

AC:

AN:

41548

American (AMR)

AF:

0.00314

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00189

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00594

AC:

404

AN:

68024

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

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

ClinVar submissions

Significance:Likely benign

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

Pathogenic

0.98

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.36

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.0043

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.60

PhyloP100

5.0

PROVEAN

Pathogenic

-6.8

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.75

MVP

0.55

MPC

0.50

ClinPred

0.11

GERP RS

0.37

Varity_R

0.82

gMVP

0.86

Mutation Taster

=64/36

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over