chr1-184708330-G-A

Variant names:

• chr1-184708330-G-A
• rs3736757
• NM_025191.4:c.1860C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 27 publications found

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)

ACMG classification

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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDEM3	NM_025191.4	MANE Select	c.1860C>T	p.Ile620Ile	synonymous	Exon 17 of 20	NP_079467.3
	EDEM3	NM_001319960.2		c.1860C>T	p.Ile620Ile	synonymous	Exon 17 of 21	NP_001306889.1
	EDEM3	NR_135118.2		n.2072C>T		non_coding_transcript_exon	Exon 17 of 21

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDEM3	ENST00000318130.13	TSL:1 MANE Select	c.1860C>T	p.Ile620Ile	synonymous	Exon 17 of 20	ENSP00000318147.7
	EDEM3	ENST00000367512.8	TSL:1	c.1860C>T	p.Ile620Ile	synonymous	Exon 17 of 21	ENSP00000356482.4
	EDEM3	ENST00000439962.1	TSL:1	n.204C>T		non_coding_transcript_exon	Exon 3 of 8	ENSP00000390536.1

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87776 AN: 151612 Hom.: 27042 Cov.: 30

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

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.: 51 AF XY: 0.502 AC XY: 364110 AN XY: 724700

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

GnomAD4 genome AF: 0.579 AC: 87862 AN: 151732 Hom.: 27075 Cov.: 30 AF XY: 0.580 AC XY: 43021 AN XY: 74134

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	7.6
DANN	Benign	0.84
PhyloP100		-0.012
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3736757; hg19: chr1-184677464; COSMIC: COSV58922980;