3-5199538-C-T

Position:

• chr3-5199538-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014674.3(EDEM1):​c.583-54C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 1,364,250 control chromosomes in the GnomAD database, including 630,803 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 0.93 (66673 hom., cov: 32)
  • Exomes 𝑓: 0.96 (564130 hom.)
• Consequence: EDEM1 NM_014674.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.76

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDEM1	NM_014674.3	c.583-54C>T		intron_variant		ENST00000256497.9	NP_055489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDEM1	ENST00000256497.9	c.583-54C>T		intron_variant		1	NM_014674.3	ENSP00000256497.4

Frequencies

GnomAD3 genomes AF: 0.934 AC: 142106 AN: 152148 Hom.: 66633 Cov.: 32

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.975

Gnomad OTH AF: 0.956

GnomAD4 exome AF: 0.964 AC: 1168655 AN: 1211984 Hom.: 564130 AF XY: 0.963 AC XY: 589700 AN XY: 612656

Gnomad4 AFR exome AF: 0.831

Gnomad4 AMR exome AF: 0.981

Gnomad4 ASJ exome AF: 0.967

Gnomad4 EAS exome AF: 0.945

Gnomad4 SAS exome AF: 0.896

Gnomad4 FIN exome AF: 0.986

Gnomad4 NFE exome AF: 0.974

Gnomad4 OTH exome AF: 0.956

GnomAD4 genome AF: 0.934 AC: 142201 AN: 152266 Hom.: 66673 Cov.: 32 AF XY: 0.933 AC XY: 69475 AN XY: 74448

Gnomad4 AFR AF: 0.842

Gnomad4 AMR AF: 0.966

Gnomad4 ASJ AF: 0.970

Gnomad4 EAS AF: 0.936

Gnomad4 SAS AF: 0.881

Gnomad4 FIN AF: 0.988

Gnomad4 NFE AF: 0.975

Gnomad4 OTH AF: 0.951

Alfa AF: 0.955 Hom.: 15299

Bravo AF: 0.930

Asia WGS AF: 0.892 AC: 3104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.024
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs377120; hg19: chr3-5241223;