11-125572568-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004879.5(EI24):​c.41G>A​(p.Arg14Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,461,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

EI24
NM_004879.5 missense, splice_region

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.24
Variant links:
Genes affected
EI24 (HGNC:13276): (EI24 autophagy associated transmembrane protein) This gene encodes a putative tumor suppressor and has higher expression in p53-expressing cells than in control cells and is an immediate-early induction target of p53-mediated apoptosis. The encoded protein may suppress cell growth by inducing apoptotic cell death through the caspase 9 and mitochondrial pathways. This gene is located on human chromosome 11q24, a region frequently altered in cancers. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene have been defined on chromosomes 1, 3, 7, and 8. [provided by RefSeq, Feb 2014]
FEZ1 (HGNC:3659): (fasciculation and elongation protein zeta 1) This gene is an ortholog of the C. elegans unc-76 gene, which is necessary for normal axonal bundling and elongation within axon bundles. Expression of this gene in C. elegans unc-76 mutants can restore to the mutants partial locomotion and axonal fasciculation, suggesting that it also functions in axonal outgrowth. The N-terminal half of the gene product is highly acidic. Alternatively spliced transcript variants encoding different isoforms of this protein have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.24091485).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EI24NM_004879.5 linkuse as main transcriptc.41G>A p.Arg14Lys missense_variant, splice_region_variant 2/11 ENST00000278903.11
STT3A-AS1NR_132372.1 linkuse as main transcriptn.270+888C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EI24ENST00000278903.11 linkuse as main transcriptc.41G>A p.Arg14Lys missense_variant, splice_region_variant 2/111 NM_004879.5 P1O14681-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461226
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726880
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 20, 2023The c.41G>A (p.R14K) alteration is located in exon 2 (coding exon 1) of the EI24 gene. This alteration results from a G to A substitution at nucleotide position 41, causing the arginine (R) at amino acid position 14 to be replaced by a lysine (K). 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
Benign
0.091
BayesDel_addAF
Benign
-0.0059
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.015
T;T;.;.;T;.;T;T;.
Eigen
Benign
-0.19
Eigen_PC
Benign
0.043
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.79
.;.;T;T;T;T;T;T;T
M_CAP
Benign
0.0027
T
MetaRNN
Benign
0.19
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.69
N;.;.;N;N;.;.;.;.
MutationTaster
Benign
0.86
D;D;N
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.12
N;D;N;.;.;N;D;N;N
REVEL
Benign
0.25
Sift
Benign
0.43
T;.;T;.;.;T;.;T;T
Sift4G
Benign
1.0
T;.;T;T;T;T;T;T;T
Polyphen
0.0020
B;.;.;.;B;B;.;.;.
Vest4
0.22
MutPred
0.28
Gain of ubiquitination at R14 (P = 0.0276);Gain of ubiquitination at R14 (P = 0.0276);Gain of ubiquitination at R14 (P = 0.0276);Gain of ubiquitination at R14 (P = 0.0276);Gain of ubiquitination at R14 (P = 0.0276);Gain of ubiquitination at R14 (P = 0.0276);Gain of ubiquitination at R14 (P = 0.0276);Gain of ubiquitination at R14 (P = 0.0276);Gain of ubiquitination at R14 (P = 0.0276);
MVP
0.21
MPC
0.50
ClinPred
0.64
D
GERP RS
5.4
Varity_R
0.46
gMVP
0.60

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: chr11-125442464; API