Genetic Variant EDEM1:p.Gly58Val (chr3-5187978-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014674.3(EDEM1):c.173G>T(p.Gly58Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G58E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EDEM1
NM_014674.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0200

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1974976).

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.173G>T	p.Gly58Val	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.173G>T	p.Gly58Val	missense	Exon 1 of 12	ENSP00000256497.4	Q92611-1
EDEM1	ENST00000443790.1	TSL:2	n.*34G>T		non_coding_transcript_exon	Exon 1 of 2	ENSP00000394615.1	F8WE67
EDEM1	ENST00000465187.1	TSL:4	n.173G>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

133524

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1389582

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687084

African (AFR)

AF:

0.00

AC:

AN:

29600

American (AMR)

AF:

0.00

AC:

AN:

35234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24774

East Asian (EAS)

AF:

0.00

AC:

AN:

34330

South Asian (SAS)

AF:

0.00

AC:

AN:

78918

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4198

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079288

Other (OTH)

AF:

0.00

AC:

AN:

57658

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000929

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.039

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.58

M_CAP

Pathogenic

0.83

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.69

PhyloP100

0.020

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.25

REVEL

Benign

0.087

Sift

Benign

0.15

Sift4G

Benign

0.28

Polyphen

0.047

Vest4

0.21

MutPred

0.16

Loss of loop (P = 0.0603)

MVP

0.85

MPC

0.34

ClinPred

0.055

GERP RS

0.60

PromoterAI

-0.050

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.033

gMVP

0.49

Mutation Taster

=98/2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over