rs121908541
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PM5PP3_StrongPP5
The NM_003907.3(EIF2B5):c.167T>G(p.Phe56Cys) variant causes a missense change. 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 Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F56V) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 33)
Consequence
EIF2B5
NM_003907.3 missense
NM_003907.3 missense
Scores
12
5
1
Clinical Significance
Conservation
PhyloP100: 7.18
Genes affected
EIF2B5 (HGNC:3261): (eukaryotic translation initiation factor 2B subunit epsilon) This gene encodes one of five subunits of eukaryotic translation initiation factor 2B (EIF2B), a GTP exchange factor for eukaryotic initiation factor 2 and an essential regulator for protein synthesis. Mutations in this gene and the genes encoding other EIF2B subunits have been associated with leukoencephalopathy with vanishing white matter. [provided by RefSeq, Nov 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chr3-184135551-T-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 5951.Status of the report is criteria_provided_single_submitter, 1 stars.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.991
PP5
?
Variant 3-184135552-T-G is Pathogenic according to our data. Variant chr3-184135552-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 5952.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EIF2B5 | NM_003907.3 | c.167T>G | p.Phe56Cys | missense_variant | 1/16 | ENST00000648915.2 | |
EIF2B5 | XM_047449148.1 | c.167T>G | p.Phe56Cys | missense_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EIF2B5 | ENST00000648915.2 | c.167T>G | p.Phe56Cys | missense_variant | 1/16 | NM_003907.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Leukoencephalopathy with vanishing white matter 5 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 24, 2007 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;T;.;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;.;.;H
MutationTaster
Benign
A;A;A
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.;.
REVEL
Pathogenic
Sift
Pathogenic
D;D;.;.
Sift4G
Uncertain
D;D;.;.
Polyphen
D;.;.;D
Vest4
MutPred
Loss of stability (P = 0.063);Loss of stability (P = 0.063);Loss of stability (P = 0.063);Loss of stability (P = 0.063);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at