Variant 17-50536828-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017957.3(EPN3):c.272G>A(p.Arg91Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000147 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

EPN3
NM_017957.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.49

Variant links:

Genes affected

EPN3 (HGNC:18235): (epsin 3) Predicted to enable clathrin binding activity and phospholipid binding activity. Predicted to be involved in endocytosis. Located in clathrin-coated vesicle; nucleoplasm; and perinuclear region of cytoplasm. Is extrinsic component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EPN3 links:

(HGNC:):

links:

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=0.088181674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPN3	NM_017957.3 linkuse as main transcript	c.272G>A	p.Arg91Gln	missense_variant	2/10	ENST00000268933.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPN3	ENST00000268933.8 linkuse as main transcript	c.272G>A	p.Arg91Gln	missense_variant	2/10	2	NM_017957.3	P1	Q9H201-1
	ENST00000654456.1 linkuse as main transcript	n.482+1099C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000155

AC:

AN:

251344

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00120

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000148

AC:

217

AN:

1461828

Hom.:

Cov.:

AF XY:

0.000157

AC XY:

114

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00353

Gnomad4 SAS exome

AF:

0.000487

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.000138

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00271

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000772

Hom.:

Bravo

AF:

0.000110

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Jun 24, 2022

The c.272G>A (p.R91Q) alteration is located in exon 2 (coding exon 1) of the EPN3 gene. This alteration results from a G to A substitution at nucleotide position 272, causing the arginine (R) at amino acid position 91 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;T;.;T;T

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.96

D;D;D;D;D

M_CAP

Benign

0.048

MetaRNN

Benign

0.088

T;T;T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.9

M;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.4

D;D;D;D;.

REVEL

Benign

0.28

Sift

Uncertain

0.0020

D;D;T;T;.

Sift4G

Uncertain

0.0060

D;T;T;T;D

Polyphen

0.98

D;.;.;.;.

Vest4

0.55

MVP

0.66

MPC

0.59

ClinPred

0.36

GERP RS

4.2

Varity_R

0.30

gMVP

0.17

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.

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