X-24055033-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001415.4(EIF2S3):​c.65C>T​(p.Thr22Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T22A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Consequence

EIF2S3
NM_001415.4 missense

Scores

2
5
9

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 2.72
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32793728).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EIF2S3NM_001415.4 linkc.65C>T p.Thr22Ile missense_variant Exon 1 of 12 ENST00000253039.9 NP_001406.1 P41091

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EIF2S3ENST00000253039.9 linkc.65C>T p.Thr22Ile missense_variant Exon 1 of 12 1 NM_001415.4 ENSP00000253039.4 P41091
EIF2S3ENST00000423068.1 linkc.62C>T p.Thr21Ile missense_variant Exon 1 of 5 2 ENSP00000391383.1 H7BZU1
EIF2S3ENST00000487075.1 linkn.88C>T non_coding_transcript_exon_variant Exon 1 of 3 5

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
23
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

MEHMO syndrome Uncertain:1
Nov 02, 2023
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.086
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.89
D
M_CAP
Pathogenic
0.56
D
MetaRNN
Benign
0.33
T
MetaSVM
Benign
-0.73
T
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.12
Sift
Uncertain
0.029
D
Sift4G
Uncertain
0.053
T
Polyphen
0.41
B
Vest4
0.43
MutPred
0.28
Loss of disorder (P = 0.0346);
MVP
0.57
MPC
0.78
ClinPred
0.84
D
GERP RS
4.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.21
gMVP
0.72

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: rs1489555629; hg19: chrX-24073150; API