dbSNP rs139559842: EDEM3:p.Ala707Ser (chr1-184706727-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_025191.4(EDEM3):c.2119G>T(p.Ala707Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. A707T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

EDEM3
NM_025191.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.80

Publications

2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.819

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.2119G>T	p.Ala707Ser	missense	Exon 18 of 20	NP_079467.3
EDEM3	NM_001319960.2		c.2119G>T	p.Ala707Ser	missense	Exon 18 of 21	NP_001306889.1	A0A8J8YX80
EDEM3	NR_135118.2		n.2350G>T		non_coding_transcript_exon	Exon 18 of 21

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EDEM3	ENST00000318130.13	TSL:1 MANE Select	c.2119G>T	p.Ala707Ser	missense	Exon 18 of 20	ENSP00000318147.7	Q9BZQ6-1
EDEM3	ENST00000367512.8	TSL:1	c.2119G>T	p.Ala707Ser	missense	Exon 18 of 21	ENSP00000356482.4	A0A8J8YX80
EDEM3	ENST00000439962.1	TSL:1	n.463G>T		non_coding_transcript_exon	Exon 4 of 8	ENSP00000390536.1	H0Y498

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251030

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.025

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-0.80

MutationAssessor

Pathogenic

3.6

PhyloP100

7.8

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.42

Sift

Uncertain

0.021

Sift4G

Uncertain

0.058

Polyphen

1.0

Vest4

0.74

MutPred

0.70

Loss of methylation at K705 (P = 0.0925)

MVP

0.75

MPC

0.63

ClinPred

0.97

GERP RS

5.8

Varity_R

0.64

gMVP

0.79

Mutation Taster

=53/47

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

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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