Variant X-24055686-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001415.4(EIF2S3):c.133+8T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,206,576 control chromosomes in the GnomAD database, including 1 homozygotes. There are 413 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., 16 hem., cov: 23)

Exomes 𝑓: 0.0012 ( 1 hom. 397 hem. )

Consequence

EIF2S3
NM_001415.4 splice_region, intron

Scores

Splicing: ADA: 0.0005593

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0190

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant X-24055686-T-C is Benign according to our data. Variant chrX-24055686-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 210934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 16 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EIF2S3	NM_001415.4 linkuse as main transcript	c.133+8T>C		splice_region_variant, intron_variant		ENST00000253039.9	NP_001406.1	P41091

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
EIF2S3	ENST00000253039.9 linkuse as main transcript	c.133+8T>C	splice_region_variant, intron_variant	1	NM_001415.4	ENSP00000253039.4	P41091
EIF2S3	ENST00000423068.1 linkuse as main transcript	c.130+8T>C	splice_region_variant, intron_variant	2		ENSP00000391383.1	H7BZU1
EIF2S3	ENST00000487075.1 linkuse as main transcript	n.156+8T>C	splice_region_variant, intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.000562

AC:

AN:

112003

Hom.:

Cov.:

AF XY:

0.000468

AC XY:

AN XY:

34179

show subpopulations

Gnomad AFR

AF:

0.000195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000191

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000363

Gnomad FIN

AF:

0.000828

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000921

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000646

AC:

118

AN:

182671

Hom.:

AF XY:

0.000655

AC XY:

AN XY:

67139

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.000184

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000579

Gnomad FIN exome

AF:

0.000250

Gnomad NFE exome

AF:

0.00114

Gnomad OTH exome

AF:

0.000665

GnomAD4 exome

AF:

0.00116

AC:

1271

AN:

1094573

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

397

AN XY:

360043

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.000200

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000648

Gnomad4 FIN exome

AF:

0.000518

Gnomad4 NFE exome

AF:

0.00140

Gnomad4 OTH exome

AF:

0.000653

GnomAD4 genome

AF:

0.000562

AC:

AN:

112003

Hom.:

Cov.:

AF XY:

0.000468

AC XY:

AN XY:

34179

show subpopulations

Gnomad4 AFR

AF:

0.000195

Gnomad4 AMR

AF:

0.000191

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000363

Gnomad4 FIN

AF:

0.000828

Gnomad4 NFE

AF:

0.000921

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000477

Hom.:

Bravo

AF:

0.000536

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

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

Dec 04, 2017

- -

EIF2S3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 30, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.5

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00056

dbscSNV1_RF

Benign

0.0080

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