chr1-184702964-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_025191.4(EDEM3):c.2236C>T(p.Pro746Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.016 in 1,611,476 control chromosomes in the GnomAD database, including 255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 21 hom., cov: 32)

Exomes 𝑓: 0.016 ( 234 hom. )

Consequence

EDEM3
NM_025191.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.96

Publications

23 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: Benign. The variant received -10 ACMG points.

BP6

Variant 1-184702964-G-A is Benign according to our data. Variant chr1-184702964-G-A is described in ClinVar as Benign. ClinVar VariationId is 3068615.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0115 (1756/152102) while in subpopulation NFE AF = 0.0179 (1217/67986). AF 95% confidence interval is 0.0171. There are 21 homozygotes in GnomAd4. There are 858 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

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.2236C>T	p.Pro746Ser	missense	Exon 19 of 20	NP_079467.3
EDEM3	NM_001319960.2		c.2236C>T	p.Pro746Ser	missense	Exon 19 of 21	NP_001306889.1	A0A8J8YX80
EDEM3	NR_135118.2		n.2467C>T		non_coding_transcript_exon	Exon 19 of 21

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EDEM3	ENST00000318130.13	TSL:1 MANE Select	c.2236C>T	p.Pro746Ser	missense	Exon 19 of 20	ENSP00000318147.7	Q9BZQ6-1
EDEM3	ENST00000367512.8	TSL:1	c.2236C>T	p.Pro746Ser	missense	Exon 19 of 21	ENSP00000356482.4	A0A8J8YX80
EDEM3	ENST00000439962.1	TSL:1	n.580C>T		non_coding_transcript_exon	Exon 5 of 8	ENSP00000390536.1	H0Y498

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1757

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00249

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00806

Gnomad ASJ

AF:

0.0256

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00436

Gnomad FIN

AF:

0.0161

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0179

Gnomad OTH

AF:

0.0125

GnomAD2 exomes

AF:

0.0118

AC:

2927

AN:

248222

AF XY:

0.0118

show subpopulations

Gnomad AFR exome

AF:

0.00293

Gnomad AMR exome

AF:

0.00422

Gnomad ASJ exome

AF:

0.0192

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0175

Gnomad NFE exome

AF:

0.0168

Gnomad OTH exome

AF:

0.0122

GnomAD4 exome

AF:

0.0165

AC:

24077

AN:

1459374

Hom.:

234

Cov.:

AF XY:

0.0162

AC XY:

11755

AN XY:

726044

show subpopulations

African (AFR)

AF:

0.00268

AC:

AN:

33270

American (AMR)

AF:

0.00450

AC:

199

AN:

44262

Ashkenazi Jewish (ASJ)

AF:

0.0203

AC:

528

AN:

26072

East Asian (EAS)

AF:

0.00

AC:

AN:

39478

South Asian (SAS)

AF:

0.00673

AC:

579

AN:

86002

European-Finnish (FIN)

AF:

0.0166

AC:

885

AN:

53328

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0189

AC:

20978

AN:

1110930

Other (OTH)

AF:

0.0134

AC:

808

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

1148

2296

3443

4591

5739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.0115

AC:

1756

AN:

152102

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

858

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.00248

AC:

103

AN:

41484

American (AMR)

AF:

0.00805

AC:

123

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0256

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.00437

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.0161

AC:

170

AN:

10584

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0179

AC:

1217

AN:

67986

Other (OTH)

AF:

0.0123

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

171

257

342

428

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0157

Hom.:

Bravo

AF:

0.0102

TwinsUK

AF:

0.0183

AC:

ALSPAC

AF:

0.0202

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.0165

AC:

142

ExAC

AF:

0.0116

AC:

1404

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0130

EpiControl

AF:

0.0146

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital disorder of glycosylation, type 2v (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0096

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

8.0

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.24

Sift

Benign

0.18

Sift4G

Benign

0.24

Polyphen

0.75

Vest4

0.43

MPC

0.41

ClinPred

0.020

GERP RS

5.2

Varity_R

0.28

gMVP

0.76

Mutation Taster

=69/31

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.26

Position offset: 32

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