19-16377132-T-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001258374.3(EPS15L1):​c.2370A>T​(p.Lys790Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,604,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

EPS15L1
NM_001258374.3 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.498
Variant links:
Genes affected
EPS15L1 (HGNC:24634): (epidermal growth factor receptor pathway substrate 15 like 1) Enables cadherin binding activity. Predicted to be involved in endocytosis and endosomal transport. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1838623).
BS2
High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EPS15L1NM_001258374.3 linkuse as main transcriptc.2370A>T p.Lys790Asn missense_variant 22/24 ENST00000455140.7 NP_001245303.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EPS15L1ENST00000455140.7 linkuse as main transcriptc.2370A>T p.Lys790Asn missense_variant 22/242 NM_001258374.3 ENSP00000393313 P1Q9UBC2-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152114
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000124
AC:
3
AN:
242516
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
131450
show subpopulations
Gnomad AFR exome
AF:
0.0000634
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:
0.00000901
Gnomad OTH exome
AF:
0.000172
GnomAD4 exome
AF:
0.0000158
AC:
23
AN:
1452752
Hom.:
0
Cov.:
31
AF XY:
0.0000166
AC XY:
12
AN XY:
722654
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:
0.0000207
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152114
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
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
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

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 GeneticsDec 21, 2022The c.2370A>T (p.K790N) alteration is located in exon 22 (coding exon 22) of the EPS15L1 gene. This alteration results from a A to T substitution at nucleotide position 2370, causing the lysine (K) at amino acid position 790 to be replaced by an asparagine (N). 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
0.75
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.049
.;T
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.60
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.3
M;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.13
Sift
Benign
0.28
T;T
Sift4G
Benign
0.49
T;T
Polyphen
0.88
.;P
Vest4
0.40
MutPred
0.35
Loss of methylation at K790 (P = 9e-04);Loss of methylation at K790 (P = 9e-04);
MVP
0.61
MPC
0.12
ClinPred
0.14
T
GERP RS
-2.4
Varity_R
0.13
gMVP
0.28

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: rs146083535; hg19: chr19-16487943; API