Genetic Variant NM_014674.3:c.358G>T (chr3-5188163-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014674.3(EDEM1):c.358G>T(p.Gly120Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,548,788 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G120S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

EDEM1
NM_014674.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.179

Publications

0 publications found

Variant links:

Genes affected

EDEM1 (HGNC:18967): (ER degradation enhancing alpha-mannosidase like protein 1) Enables mannosyl-oligosaccharide 1,2-alpha-mannosidase activity and misfolded protein binding activity. Involved in mannose trimming involved in glycoprotein ERAD pathway; positive regulation of retrograde protein transport, ER to cytosol; and protein targeting to ER. Located in aggresome and endoplasmic reticulum quality control compartment. [provided by Alliance of Genome Resources, Apr 2022]

EDEM1 links:

ENSG00000233912 (HGNC:):

ENSG00000233912 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014707357).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014674.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDEM1	NM_014674.3	MANE Select	c.358G>T	p.Gly120Cys	missense	Exon 1 of 12	NP_055489.1	Q92611-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EDEM1	ENST00000256497.9	TSL:1 MANE Select	c.358G>T	p.Gly120Cys	missense	Exon 1 of 12	ENSP00000256497.4	Q92611-1
EDEM1	ENST00000443790.1	TSL:2	n.*219G>T		non_coding_transcript_exon	Exon 1 of 2	ENSP00000394615.1	F8WE67
EDEM1	ENST00000465187.1	TSL:4	n.358G>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152010

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:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000141

AC:

AN:

149436

AF XY:

0.000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00207

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000179

AC:

AN:

1396778

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

690448

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30028

American (AMR)

AF:

0.00

AC:

AN:

35730

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24884

East Asian (EAS)

AF:

0.000634

AC:

AN:

34720

South Asian (SAS)

AF:

0.00

AC:

AN:

78616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

9.25e-7

AC:

AN:

1080606

Other (OTH)

AF:

0.0000345

AC:

AN:

57928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.0000395

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41408

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67950

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.00

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.000153

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.067

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.70

M_CAP

Pathogenic

0.96

MetaRNN

Benign

0.015

MetaSVM

Benign

-0.52

MutationAssessor

Benign

0.34

PhyloP100

0.18

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.30

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.019

Polyphen

0.97

Vest4

0.21

MutPred

0.44

Loss of disorder (P = 0.0204)

MVP

0.87

MPC

0.41

ClinPred

0.16

GERP RS

-3.6

PromoterAI

-0.094

Neutral

(source)

Varity_R

0.18

gMVP

0.72

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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