chr11-125577510-C-T

Position:

chr11-125577510-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004879.5(EI24):c.256C>T(p.Leu86Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

EI24
NM_004879.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.28

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]

EI24 links:

STT3A-AS1 (HGNC:):

STT3A-AS1 links:

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]

FEZ1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EI24	NM_004879.5 linkuse as main transcript	c.256C>T	p.Leu86Phe	missense_variant	5/11	ENST00000278903.11
STT3A-AS1	NR_132372.1 linkuse as main transcript	n.152-3936G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EI24	ENST00000278903.11 linkuse as main transcript	c.256C>T	p.Leu86Phe	missense_variant	5/11	1	NM_004879.5	P1	O14681-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

248974

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135078

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461276

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726922

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000564

Hom.:

ExAC

AF:

0.00000828

AC:

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 submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.256C>T (p.L86F) alteration is located in exon 5 (coding exon 4) of the EI24 gene. This alteration results from a C to T substitution at nucleotide position 256, causing the leucine (L) at amino acid position 86 to be replaced by a phenylalanine (F). 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

0.85

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

T;.;.;T;.;T;T;.

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

.;D;D;D;D;D;D;D

M_CAP

Benign

0.036

MetaRNN

Pathogenic

0.78

D;D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.15

MutationAssessor

Uncertain

2.2

M;.;.;M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.2

N;N;.;.;N;.;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.012

D;D;.;.;D;.;D;D

Sift4G

Uncertain

0.020

D;D;D;D;D;D;D;D

Polyphen

1.0

D;.;.;D;D;.;.;.

Vest4

0.77

MutPred

0.62

Loss of stability (P = 0.0722);.;.;Loss of stability (P = 0.0722);Loss of stability (P = 0.0722);Loss of stability (P = 0.0722);.;Loss of stability (P = 0.0722);

MVP

0.41

MPC

1.4

ClinPred

0.74

GERP RS

5.6

Varity_R

0.40

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over