Menu
GeneBe

X-24055668-A-G

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.Thr41=) 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

2

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.433 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Hemizygotes in GnomAd at 54 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EIF2S3NM_001415.4 linkuse as main transcriptc.123A>G p.Thr41= synonymous_variant 2/12 ENST00000253039.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EIF2S3ENST00000253039.9 linkuse as main transcriptc.123A>G p.Thr41= synonymous_variant 2/121 NM_001415.4 P1
EIF2S3ENST00000423068.1 linkuse as main transcriptc.123A>G p.Thr41= synonymous_variant 2/52
EIF2S3ENST00000487075.1 linkuse as main transcriptn.146A>G non_coding_transcript_exon_variant 2/35

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00189
AC:
212
AN:
112347
Hom.:
0
Cov.:
23
AF XY:
0.00157
AC XY:
54
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:
90
AN:
183382
Hom.:
0
AF XY:
0.000295
AC XY:
20
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.:
0
Cov.:
31
AF XY:
0.000248
AC XY:
90
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00189
AC:
212
AN:
112401
Hom.:
0
Cov.:
23
AF XY:
0.00156
AC XY:
54
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.:
5
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 submitterclinical testingGenetic Services Laboratory, University of ChicagoJul 25, 2017- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 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.

Other links and lift over

dbSNP: rs56229020; hg19: chrX-24073785; API