3-5219976-T-C

Variant names:

• chr3-5219976-T-C
• rs457712
• NM_014674.3:c.*4058T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014674.3(EDEM1):​c.*4058T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 152,358 control chromosomes in the GnomAD database, including 67,638 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 0.94 (67604 hom., cov: 33)
  • Exomes 𝑓: 0.96 (34 hom.)
• Consequence: EDEM1 NM_014674.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

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.*4058T>C		downstream_gene	N/A	NP_055489.1	Q92611-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDEM1	ENST00000256497.9	TSL:1 MANE Select	c.*4058T>C		downstream_gene	N/A	ENSP00000256497.4	Q92611-1

Frequencies

GnomAD3 genomes AF: 0.941 AC: 143174 AN: 152166 Hom.: 67568 Cov.: 33

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.962

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.962

GnomAD4 exome AF: 0.959 AC: 71 AN: 74 Hom.: 34 Cov.: 0 AF XY: 0.979 AC XY: 47 AN XY: 48

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.958 AC: 69 AN: 72

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.941 AC: 143267 AN: 152284 Hom.: 67604 Cov.: 33 AF XY: 0.939 AC XY: 69901 AN XY: 74450

African (AFR) AF: 0.861 AC: 35772 AN: 41538

American (AMR) AF: 0.974 AC: 14902 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 3378 AN: 3472

East Asian (EAS) AF: 0.927 AC: 4810 AN: 5188

South Asian (SAS) AF: 0.877 AC: 4226 AN: 4818

European-Finnish (FIN) AF: 0.962 AC: 10208 AN: 10612

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.981 AC: 66753 AN: 68038

Other (OTH) AF: 0.957 AC: 2026 AN: 2116

Alfa AF: 0.964 Hom.: 92944

Bravo AF: 0.940

Asia WGS AF: 0.887 AC: 3087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.71
PhyloP100		-1.4
Mutation Taster		=94/6	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs457712; hg19: chr3-5261661;