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GeneBe

3-150568213-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_032025.5(EIF2A):c.732C>A(p.Asp244Glu) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

EIF2A
NM_032025.5 missense

Scores

5
10
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73
Variant links:
Genes affected
EIF2A (HGNC:3254): (eukaryotic translation initiation factor 2A) This gene encodes a eukaryotic translation initiation factor that catalyzes the formation of puromycin-sensitive 80 S preinitiation complexes and the poly(U)-directed synthesis of polyphenylalanine at low concentrations of Mg2+. This gene should not be confused with eIF2-alpha (EIF2S1, Gene ID: 1965), the alpha subunit of the eIF2 translation initiation complex. Although both of these proteins function in binding initiator tRNA to the 40 S ribosomal subunit, the encoded protein does so in a codon-dependent manner, whereas eIF2 complex requires GTP. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]
SERP1 (HGNC:10759): (stress associated endoplasmic reticulum protein 1) Predicted to be involved in endoplasmic reticulum unfolded protein response and protein glycosylation. Predicted to act upstream of or within several processes, including multicellular organism aging; positive regulation of organ growth; and positive regulation of peptide hormone secretion. Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.927

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EIF2ANM_032025.5 linkuse as main transcriptc.732C>A p.Asp244Glu missense_variant 9/14 ENST00000460851.6
LOC124900547XR_007096128.1 linkuse as main transcriptn.241-1107G>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EIF2AENST00000460851.6 linkuse as main transcriptc.732C>A p.Asp244Glu missense_variant 9/141 NM_032025.5 P3Q9BY44-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 26, 2022The c.732C>A (p.D244E) alteration is located in exon 9 (coding exon 9) of the EIF2A gene. This alteration results from a C to A substitution at nucleotide position 732, causing the aspartic acid (D) at amino acid position 244 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
Cadd
Pathogenic
27
Dann
Uncertain
1.0
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D;D;D;D
M_CAP
Benign
0.057
D
MetaRNN
Pathogenic
0.93
D;D;D;D
MetaSVM
Uncertain
-0.095
T
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-3.8
D;D;D;D
REVEL
Uncertain
0.46
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Uncertain
0.0060
D;D;D;D
Polyphen
1.0
.;D;.;.
Vest4
0.82
MutPred
0.87
.;Loss of glycosylation at S240 (P = 0.0536);.;.;
MVP
0.64
MPC
0.53
ClinPred
0.99
D
GERP RS
6.0
Varity_R
0.77
gMVP
0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-150286000; API