dbSNP rs3736757: EDEM3:p.Ile620Ile (chr1-184708330-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_025191.4(EDEM3):c.1860C>T(p.Ile620Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,608,790 control chromosomes in the GnomAD database, including 213,410 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 27075 hom., cov: 30)

Exomes 𝑓: 0.50 ( 186335 hom. )

Consequence

EDEM3
NM_025191.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0120

Publications

27 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: 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP7

Synonymous conserved (PhyloP=-0.012 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDEM3	NM_025191.4 link	c.1860C>T	p.Ile620Ile	synonymous_variant	Exon 17 of 20	ENST00000318130.13	NP_079467.3	Q9BZQ6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EDEM3	ENST00000318130.13 link	c.1860C>T	p.Ile620Ile	synonymous_variant	Exon 17 of 20	1	NM_025191.4	ENSP00000318147.7		Q9BZQ6-1

Frequencies

GnomAD3 genomes

AF:

0.579

AC:

87776

AN:

151612

Hom.:

27042

Cov.:

show subpopulations

Gnomad AFR

AF:

0.803

Gnomad AMI

AF:

0.535

Gnomad AMR

AF:

0.501

Gnomad ASJ

AF:

0.465

Gnomad EAS

AF:

0.680

Gnomad SAS

AF:

0.608

Gnomad FIN

AF:

0.518

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.467

Gnomad OTH

AF:

0.559

GnomAD2 exomes

AF:

0.526

AC:

129518

AN:

246424

AF XY:

0.524

show subpopulations

Gnomad AFR exome

AF:

0.809

Gnomad AMR exome

AF:

0.461

Gnomad ASJ exome

AF:

0.460

Gnomad EAS exome

AF:

0.689

Gnomad FIN exome

AF:

0.512

Gnomad NFE exome

AF:

0.467

Gnomad OTH exome

AF:

0.512

GnomAD4 exome

AF:

0.501

AC:

729520

AN:

1457058

Hom.:

186335

Cov.:

AF XY:

0.502

AC XY:

364110

AN XY:

724700

show subpopulations

African (AFR)

AF:

0.815

AC:

26980

AN:

33090

American (AMR)

AF:

0.465

AC:

20160

AN:

43350

Ashkenazi Jewish (ASJ)

AF:

0.460

AC:

11943

AN:

25990

East Asian (EAS)

AF:

0.653

AC:

25885

AN:

39612

South Asian (SAS)

AF:

0.598

AC:

50812

AN:

84918

European-Finnish (FIN)

AF:

0.508

AC:

27133

AN:

53382

Middle Eastern (MID)

AF:

0.557

AC:

3203

AN:

5752

European-Non Finnish (NFE)

AF:

0.479

AC:

531887

AN:

1110740

Other (OTH)

AF:

0.523

AC:

31517

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

18780

37561

56341

75122

93902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16012

32024

48036

64048

80060

<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:

0.579

AC:

87862

AN:

151732

Hom.:

27075

Cov.:

AF XY:

0.580

AC XY:

43021

AN XY:

74134

show subpopulations

African (AFR)

AF:

0.803

AC:

33280

AN:

41428

American (AMR)

AF:

0.501

AC:

7630

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.465

AC:

1608

AN:

3460

East Asian (EAS)

AF:

0.680

AC:

3500

AN:

5144

South Asian (SAS)

AF:

0.607

AC:

2914

AN:

4800

European-Finnish (FIN)

AF:

0.518

AC:

5426

AN:

10478

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.467

AC:

31691

AN:

67896

Other (OTH)

AF:

0.555

AC:

1168

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1716

3433

5149

6866

8582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<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:

0.506

Hom.:

73530

Bravo

AF:

0.588

Asia WGS

AF:

0.632

AC:

2198

AN:

3476

EpiCase

AF:

0.470

EpiControl

AF:

0.471

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.6

(source)

DANN

Benign

0.84

PhyloP100

-0.012

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over