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GeneBe

X-24054996-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001415.4(EIF2S3):c.28C>T(p.Leu10=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000251 in 1,209,117 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 104 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., 5 hem., cov: 23)
Exomes 𝑓: 0.00026 ( 0 hom. 99 hem. )

Consequence

EIF2S3
NM_001415.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.90
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 -15 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=-0.39).
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-24054996-C-T is Benign according to our data. Variant chrX-24054996-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 810535.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
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=2.9 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 5 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EIF2S3NM_001415.4 linkuse as main transcriptc.28C>T p.Leu10= synonymous_variant 1/12 ENST00000253039.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EIF2S3ENST00000253039.9 linkuse as main transcriptc.28C>T p.Leu10= synonymous_variant 1/121 NM_001415.4 P1
EIF2S3ENST00000423068.1 linkuse as main transcriptc.28C>T p.Leu10= synonymous_variant 1/52
EIF2S3ENST00000487075.1 linkuse as main transcriptn.51C>T non_coding_transcript_exon_variant 1/35

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000206
AC:
23
AN:
111463
Hom.:
0
Cov.:
23
AF XY:
0.000149
AC XY:
5
AN XY:
33649
show subpopulations
Gnomad AFR
AF:
0.0000978
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000955
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:
0.000358
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000110
AC:
20
AN:
181040
Hom.:
0
AF XY:
0.000166
AC XY:
11
AN XY:
66302
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000105
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000223
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000255
AC:
280
AN:
1097654
Hom.:
0
Cov.:
30
AF XY:
0.000273
AC XY:
99
AN XY:
363200
show subpopulations
Gnomad4 AFR exome
AF:
0.000114
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000554
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000289
Gnomad4 OTH exome
AF:
0.000521
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000206
AC:
23
AN:
111463
Hom.:
0
Cov.:
23
AF XY:
0.000149
AC XY:
5
AN XY:
33649
show subpopulations
Gnomad4 AFR
AF:
0.0000978
Gnomad4 AMR
AF:
0.0000955
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000358
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000521
Hom.:
6
Bravo
AF:
0.000200
EpiCase
AF:
0.000818
EpiControl
AF:
0.000178

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoJun 01, 2021- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenOct 01, 2022EIF2S3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
Cadd
Benign
6.6
Dann
Benign
0.93

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: rs148505917; hg19: chrX-24073113; API