Genetic Variant NM_001981.3:c.1880G>T (chr1-51402437-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001981.3(EPS15):c.1880G>T(p.Gly627Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G627D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EPS15
NM_001981.3 missense, splice_region

Scores

Splicing: ADA: 0.08945

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.66

Publications

0 publications found

Variant links:

Genes affected

EPS15 (HGNC:3419): (epidermal growth factor receptor pathway substrate 15) This gene encodes a protein that is part of the EGFR pathway. The protein is present at clatherin-coated pits and is involved in receptor-mediated endocytosis of EGF. Notably, this gene is rearranged with the HRX/ALL/MLL gene in acute myelogeneous leukemias. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2009]

EPS15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2748559).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001981.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EPS15	NM_001981.3	MANE Select	c.1880G>T	p.Gly627Val	missense splice_region	Exon 18 of 25	NP_001972.1	P42566-1
EPS15	NM_001410797.1		c.1991G>T	p.Gly664Val	missense splice_region	Exon 18 of 25	NP_001397726.1	A0A994J5A3
EPS15	NM_001410796.1		c.1790G>T	p.Gly597Val	missense splice_region	Exon 17 of 24	NP_001397725.1	A0A994J5J3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EPS15	ENST00000371733.8	TSL:1 MANE Select	c.1880G>T	p.Gly627Val	missense splice_region	Exon 18 of 25	ENSP00000360798.3	P42566-1
EPS15	ENST00000371730.6	TSL:1	c.1478G>T	p.Gly493Val	missense splice_region	Exon 16 of 23	ENSP00000360795.2	B1AUU8
EPS15	ENST00000706292.1		c.1991G>T	p.Gly664Val	missense splice_region	Exon 18 of 25	ENSP00000516336.1	A0A994J5A3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

229832

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1381324

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689244

African (AFR)

AF:

0.00

AC:

AN:

30778

American (AMR)

AF:

0.00

AC:

AN:

38738

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24574

East Asian (EAS)

AF:

0.00

AC:

AN:

38468

South Asian (SAS)

AF:

0.00

AC:

AN:

77328

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52188

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4980

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1057206

Other (OTH)

AF:

0.00

AC:

AN:

57064

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.067

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.022

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

2.7

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.13

Sift

Uncertain

0.024

Sift4G

Uncertain

0.047

Polyphen

0.98

Vest4

0.58

MutPred

0.16

Gain of glycosylation at S622 (P = 0.1475)

MVP

0.55

MPC

0.24

ClinPred

0.94

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.60

gMVP

0.24

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.089

dbscSNV1_RF

Benign

0.29

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over