rs3736757

Positions:

• chr1-184708330-G-A
• chr1-184708330-G-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
EDEM3	NM_025191.4	c.1860C>T	p.Ile620Ile	synonymous_variant	17/20	ENST00000318130.13	NP_079467.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDEM3	ENST00000318130.13	c.1860C>T	p.Ile620Ile	synonymous_variant	17/20	1	NM_025191.4	ENSP00000318147.7

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

GnomAD3 exomes AF: 0.526 AC: 129518 AN: 246424 Hom.: 35527 AF XY: 0.524 AC XY: 69689 AN XY: 133110

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 SAS exome AF: 0.601

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

Gnomad4 AFR exome AF: 0.815

Gnomad4 AMR exome AF: 0.465

Gnomad4 ASJ exome AF: 0.460

Gnomad4 EAS exome AF: 0.653

Gnomad4 SAS exome AF: 0.598

Gnomad4 FIN exome AF: 0.508

Gnomad4 NFE exome AF: 0.479

Gnomad4 OTH exome AF: 0.523

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

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.555

Alfa AF: 0.486 Hom.: 42434

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
DANN	Benign	0.84

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

LitVar

Other links and lift over

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