19-55079834-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_133180.3(EPS8L1):​c.262C>T​(p.Leu88Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,766 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

EPS8L1
NM_133180.3 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23
Variant links:
Genes affected
EPS8L1 (HGNC:21295): (EPS8 signaling adaptor L1) This gene encodes a protein that is related to epidermal growth factor receptor pathway substrate 8 (EPS8), a substrate for the epidermal growth factor receptor. The function of this protein is unknown. At least two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EPS8L1NM_133180.3 linkc.262C>T p.Leu88Phe missense_variant Exon 5 of 20 ENST00000201647.11 NP_573441.2 Q8TE68-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EPS8L1ENST00000201647.11 linkc.262C>T p.Leu88Phe missense_variant Exon 5 of 20 1 NM_133180.3 ENSP00000201647.5 Q8TE68-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000162
AC:
4
AN:
247068
Hom.:
0
AF XY:
0.0000224
AC XY:
3
AN XY:
133856
show subpopulations
Gnomad AFR exome
AF:
0.0000630
Gnomad AMR exome
AF:
0.00
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:
0.0000269
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1460766
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
726614
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000313
Hom.:
0
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 12, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.262C>T (p.L88F) alteration is located in exon 5 (coding exon 4) of the EPS8L1 gene. This alteration results from a C to T substitution at nucleotide position 262, causing the leucine (L) at amino acid position 88 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
Benign
0.22
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.41
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.10
T;T;T
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.72
T;T;T
M_CAP
Benign
0.060
D
MetaRNN
Uncertain
0.46
T;T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
1.7
.;L;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-2.1
.;N;N
REVEL
Benign
0.22
Sift
Benign
0.064
.;T;T
Sift4G
Benign
0.20
T;T;T
Polyphen
1.0
.;D;D
Vest4
0.38
MVP
0.36
MPC
0.85
ClinPred
0.76
D
GERP RS
4.0
Varity_R
0.15
gMVP
0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs143589639; hg19: chr19-55591202; API