rs113994026
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_020365.5(EIF2B3):c.1193_1194delTG(p.Val398GlyfsTer35) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
EIF2B3
NM_020365.5 frameshift
NM_020365.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.16
Publications
1 publications found
Genes affected
EIF2B3 (HGNC:3259): (eukaryotic translation initiation factor 2B subunit gamma) The protein encoded by this gene is one of the subunits of initiation factor eIF2B, which catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. It has also been found to function as a cofactor of hepatitis C virus internal ribosome entry site-mediated translation. Mutations in this gene have been associated with leukodystrophy with vanishing white matter. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
EIF2B3 Gene-Disease associations (from GenCC):
- leukoencephalopathy with vanishing white matter 3Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- leukoencephalopathy with vanishing white matterInheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
- leukoencephalopathy with vanishing white matter 1Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- ovarioleukodystrophyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 1-44874685-CCA-C is Pathogenic according to our data. Variant chr1-44874685-CCA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 4438.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_020365.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| EIF2B3 | MANE Select | c.1193_1194delTG | p.Val398GlyfsTer35 | frameshift | Exon 10 of 12 | NP_065098.1 | Q9NR50-1 | ||
| EIF2B3 | c.1193_1194delTG | p.Val398GlyfsTer31 | frameshift | Exon 10 of 10 | NP_001160060.1 | Q9NR50-2 | |||
| EIF2B3 | c.1193_1194delTG | p.Val398GlyfsTer7 | frameshift | Exon 10 of 11 | NP_001248347.1 | Q9NR50-3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| EIF2B3 | TSL:1 MANE Select | c.1193_1194delTG | p.Val398GlyfsTer35 | frameshift | Exon 10 of 12 | ENSP00000353575.2 | Q9NR50-1 | ||
| EIF2B3 | TSL:1 | c.1193_1194delTG | p.Val398GlyfsTer31 | frameshift | Exon 10 of 10 | ENSP00000361257.3 | Q9NR50-2 | ||
| EIF2B3 | TSL:1 | c.1193_1194delTG | p.Val398GlyfsTer7 | frameshift | Exon 10 of 11 | ENSP00000483996.1 | Q9NR50-3 |
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152172Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152172
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461872Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727232 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461872
Hom.:
AF XY:
AC XY:
1
AN XY:
727232
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111998
Other (OTH)
AF:
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000131 AC: 2AN: 152172Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74330 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152172
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
74330
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41442
American (AMR)
AF:
AC:
0
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5202
South Asian (SAS)
AF:
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
2
AN:
68030
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Leukoencephalopathy with vanishing white matter 3 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
Publications
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