Variant X-24055644-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001415.4(EIF2S3):c.99C>T(p.His33=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 111,034 control chromosomes in the GnomAD database, including 12,202 homozygotes. There are 16,879 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 12202 hom., 16879 hem., cov: 23)

Exomes 𝑓: 0.64 ( 160287 hom. 226881 hem. )

Failed GnomAD Quality Control

Consequence

EIF2S3
NM_001415.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0870

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant X-24055644-C-T is Benign according to our data. Variant chrX-24055644-C-T is described in ClinVar as [Benign]. Clinvar id is 128994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-24055644-C-T is described in Lovd as [Benign]. Variant chrX-24055644-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.087 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EIF2S3	NM_001415.4 linkuse as main transcript	c.99C>T	p.His33=	synonymous_variant	2/12	ENST00000253039.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
EIF2S3	ENST00000253039.9 linkuse as main transcript	c.99C>T	p.His33=	synonymous_variant	2/12	1	NM_001415.4	P1
EIF2S3	ENST00000423068.1 linkuse as main transcript	c.99C>T	p.His33=	synonymous_variant	2/5	2
EIF2S3	ENST00000487075.1 linkuse as main transcript	n.122C>T		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.510

AC:

56639

AN:

110981

Hom.:

12204

Cov.:

AF XY:

0.508

AC XY:

16870

AN XY:

33223

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.796

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.623

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.693

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.523

GnomAD3 exomes

AF:

0.565

AC:

103230

AN:

182577

Hom.:

20814

AF XY:

0.554

AC XY:

37187

AN XY:

67143

show subpopulations

Gnomad AFR exome

AF:

0.164

Gnomad AMR exome

AF:

0.620

Gnomad ASJ exome

AF:

0.620

Gnomad EAS exome

AF:

0.413

Gnomad SAS exome

AF:

0.238

Gnomad FIN exome

AF:

0.695

Gnomad NFE exome

AF:

0.681

Gnomad OTH exome

AF:

0.612

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.640

AC:

702664

AN:

1097130

Hom.:

160287

Cov.:

AF XY:

0.625

AC XY:

226881

AN XY:

363002

show subpopulations

Gnomad4 AFR exome

AF:

0.162

Gnomad4 AMR exome

AF:

0.619

Gnomad4 ASJ exome

AF:

0.630

Gnomad4 EAS exome

AF:

0.389

Gnomad4 SAS exome

AF:

0.245

Gnomad4 FIN exome

AF:

0.695

Gnomad4 NFE exome

AF:

0.692

Gnomad4 OTH exome

AF:

0.595

GnomAD4 genome

AF:

0.510

AC:

56630

AN:

111034

Hom.:

12202

Cov.:

AF XY:

0.507

AC XY:

16879

AN XY:

33286

show subpopulations

Gnomad4 AFR

AF:

0.177

Gnomad4 AMR

AF:

0.599

Gnomad4 ASJ

AF:

0.623

Gnomad4 EAS

AF:

0.361

Gnomad4 SAS

AF:

0.222

Gnomad4 FIN

AF:

0.693

Gnomad4 NFE

AF:

0.681

Gnomad4 OTH

AF:

0.518

Alfa

AF:

0.592

Hom.:

6823

Bravo

AF:

0.497

EpiCase

AF:

0.677

EpiControl

AF:

0.678

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2021

- -

MEHMO syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

4.2

DANN

Benign

0.80

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