Variant 12-10506307-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_001357734.3(EIF2S3B):c.405T>C(p.Cys135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000918 in 1,614,142 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00094 ( 8 hom. )

Consequence

EIF2S3B
NM_001357734.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.95

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 12-10506307-T-C is Benign according to our data. Variant chr12-10506307-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2642700.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.95 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
EIF2S3B	NM_001357734.3 linkuse as main transcript	c.405T>C	p.Cys135=	synonymous_variant	1/1	ENST00000538173.2
LOC105369657	XR_931355.4 linkuse as main transcript	n.443-5706A>G		intron_variant, non_coding_transcript_variant
EIF2S3B	NM_001357731.1 linkuse as main transcript	c.405T>C	p.Cys135=	synonymous_variant	1/2
LOC105369657	XR_001749003.3 linkuse as main transcript	n.443-5706A>G		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.405T>C	p.Cys135=	synonymous_variant	1/1		NM_001357734.3	P1	Q2VIR3-1
EIF2S3B	ENST00000322446.3 linkuse as main transcript	c.405T>C	p.Cys135=	synonymous_variant	1/2	1			Q2VIR3-2

Frequencies

GnomAD3 genomes

AF:

0.000670

AC:

102

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00560

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00125

AC:

315

AN:

251492

Hom.:

AF XY:

0.00167

AC XY:

227

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00676

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000809

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000943

AC:

1379

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

847

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00705

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000611

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.000670

AC:

102

AN:

152278

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000753

Hom.:

Bravo

AF:

0.000544

EpiCase

AF:

0.000818

EpiControl

AF:

0.000948

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

May 01, 2022

EIF2S3B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

Cadd

Benign

8.5

Dann

Benign

0.56

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