NM_025191.4:c.1858A>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_025191.4(EDEM3):c.1858A>G(p.Ile620Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,609,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I620T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

EDEM3
NM_025191.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59

Publications

4 publications found

Variant links:

Genes affected

EDEM3 (HGNC:16787): (ER degradation enhancing alpha-mannosidase like protein 3) Quality control in the endoplasmic reticulum (ER) ensures that only properly folded proteins are retained in the cell through recognition and degradation of misfolded or unassembled proteins. EDEM3 belongs to a group of proteins that accelerate degradation of misfolded glycoproteins in the ER (Hirao et al., 2006 [PubMed 16431915]).[supplied by OMIM, Mar 2008]

EDEM3 Gene-Disease associations (from GenCC):

congenital disorder of glycosylation, type 2v
Inheritance: AR Classification: STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)

EDEM3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05519244).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000112 (17/152132) while in subpopulation NFE AF = 0.000206 (14/68026). AF 95% confidence interval is 0.000124. There are 0 homozygotes in GnomAd4. There are 8 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025191.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EDEM3	NM_025191.4	MANE Select	c.1858A>G	p.Ile620Val	missense	Exon 17 of 20	NP_079467.3
EDEM3	NM_001319960.2		c.1858A>G	p.Ile620Val	missense	Exon 17 of 21	NP_001306889.1	A0A8J8YX80
EDEM3	NR_135118.2		n.2070A>G		non_coding_transcript_exon	Exon 17 of 21

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EDEM3	ENST00000318130.13	TSL:1 MANE Select	c.1858A>G	p.Ile620Val	missense	Exon 17 of 20	ENSP00000318147.7	Q9BZQ6-1
EDEM3	ENST00000367512.8	TSL:1	c.1858A>G	p.Ile620Val	missense	Exon 17 of 21	ENSP00000356482.4	A0A8J8YX80
EDEM3	ENST00000439962.1	TSL:1	n.202A>G		non_coding_transcript_exon	Exon 3 of 8	ENSP00000390536.1	H0Y498

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000769

AC:

AN:

247074

AF XY:

0.0000824

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.0000600

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000133

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000988

AC:

144

AN:

1457736

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

725060

show subpopulations

African (AFR)

AF:

0.0000605

AC:

AN:

33076

American (AMR)

AF:

0.0000460

AC:

AN:

43502

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26006

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.0000235

AC:

AN:

85030

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.000121

AC:

134

AN:

1111062

Other (OTH)

AF:

0.0000332

AC:

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000112

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000148

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0063

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.84

M_CAP

Benign

0.0041

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

PhyloP100

1.6

PrimateAI

Benign

0.40

PROVEAN

Benign

0.36

REVEL

Benign

0.084

Sift

Benign

0.30

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.022

MVP

0.51

MPC

0.13

ClinPred

0.027

GERP RS

0.054

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.098

Mutation Taster

=99/1

polymorphism

(source)

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over