Variant X-24055668-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001415.4(EIF2S3):c.123A>G(p.Thr41Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000445 in 1,209,861 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 144 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., 54 hem., cov: 23)

Exomes 𝑓: 0.00030 ( 0 hom. 90 hem. )

Consequence

EIF2S3
NM_001415.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.433

Variant links:

Genes affected

EIF2S3 (HGNC:3267): (eukaryotic translation initiation factor 2 subunit gamma) The protein encoded by this gene is the largest subunit of a heterotrimeric GTP-binding protein involved in the recruitment of methionyl-tRNA(i) to the 40 S ribosomal subunit. [provided by RefSeq, Jan 2010]

EIF2S3 links:

EIF2S3 (HGNC:):

EIF2S3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

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

BP6

Variant X-24055668-A-G is Benign according to our data. Variant chrX-24055668-A-G is described in ClinVar as [Benign]. Clinvar id is 784431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-24055668-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.433 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 54 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2S3	NM_001415.4 linkuse as main transcript	c.123A>G	p.Thr41Thr	synonymous_variant	2/12	ENST00000253039.9	NP_001406.1	P41091

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EIF2S3	ENST00000253039.9 linkuse as main transcript	c.123A>G	p.Thr41Thr	synonymous_variant	2/12	1	NM_001415.4	ENSP00000253039.4	P41091
EIF2S3	ENST00000423068.1 linkuse as main transcript	c.120A>G	p.Thr40Thr	synonymous_variant	2/5	2		ENSP00000391383.1	H7BZU1
EIF2S3	ENST00000487075.1 linkuse as main transcript	n.146A>G		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.00189

AC:

212

AN:

112347

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

AN XY:

34483

show subpopulations

Gnomad AFR

AF:

0.00579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00172

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:

0.000263

Gnomad OTH

AF:

0.000661

GnomAD3 exomes

AF:

0.000491

AC:

AN:

183382

Hom.:

AF XY:

0.000295

AC XY:

AN XY:

67834

show subpopulations

Gnomad AFR exome

AF:

0.00494

Gnomad AMR exome

AF:

0.000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000147

Gnomad OTH exome

AF:

0.000663

GnomAD4 exome

AF:

0.000297

AC:

326

AN:

1097460

Hom.:

Cov.:

AF XY:

0.000248

AC XY:

AN XY:

362908

show subpopulations

Gnomad4 AFR exome

AF:

0.00477

Gnomad4 AMR exome

AF:

0.000710

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000170

Gnomad4 OTH exome

AF:

0.000608

GnomAD4 genome

AF:

0.00189

AC:

212

AN:

112401

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

AN XY:

34547

show subpopulations

Gnomad4 AFR

AF:

0.00577

Gnomad4 AMR

AF:

0.00171

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000263

Gnomad4 OTH

AF:

0.000653

Alfa

AF:

0.000825

Hom.:

Bravo

AF:

0.00221

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 25, 2017

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.6

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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