chr3-5199624-C-A

Variant names:

• chr3-5199624-C-A
• rs410509
• NM_014674.3:c.615C>A

Variant summary

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

The NM_014674.3(EDEM1):​c.615C>A​(p.Ala205Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.965 in 1,613,392 control chromosomes in the GnomAD database, including 752,632 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 0.95 (68148 hom., cov: 33)
  • Exomes 𝑓: 0.97 (684484 hom.)
• Consequence: EDEM1 NM_014674.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 16 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=-1.95 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.969 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.615C>A	p.Ala205Ala	synonymous	Exon 3 of 12	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.615C>A	p.Ala205Ala	synonymous	Exon 3 of 12	ENSP00000256497.4	Q92611-1
	EDEM1	ENST00000445686.1	TSL:2	c.30C>A	p.Ala10Ala	synonymous	Exon 3 of 10	ENSP00000394099.1	Q92611-2
	EDEM1	ENST00000465369.5	TSL:5	n.701C>A		non_coding_transcript_exon	Exon 3 of 10

Frequencies

GnomAD3 genomes AF: 0.945 AC: 143839 AN: 152172 Hom.: 68110 Cov.: 33

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.970

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.881

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.976

Gnomad OTH AF: 0.960

GnomAD2 exomes AF: 0.959 AC: 240508 AN: 250906 AF XY: 0.958

Gnomad AFR exome AF: 0.878

Gnomad AMR exome AF: 0.985

Gnomad ASJ exome AF: 0.971

Gnomad EAS exome AF: 0.940

Gnomad FIN exome AF: 0.988

Gnomad NFE exome AF: 0.975

Gnomad OTH exome AF: 0.968

GnomAD4 exome AF: 0.968 AC: 1413686 AN: 1461102 Hom.: 684484 Cov.: 40 AF XY: 0.966 AC XY: 701952 AN XY: 726874

African (AFR) AF: 0.874 AC: 29214 AN: 33442

American (AMR) AF: 0.984 AC: 43866 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 25303 AN: 26126

East Asian (EAS) AF: 0.945 AC: 37505 AN: 39676

South Asian (SAS) AF: 0.900 AC: 77493 AN: 86098

European-Finnish (FIN) AF: 0.986 AC: 52655 AN: 53410

Middle Eastern (MID) AF: 0.973 AC: 5610 AN: 5768

European-Non Finnish (NFE) AF: 0.975 AC: 1084060 AN: 1111630

Other (OTH) AF: 0.961 AC: 57980 AN: 60358

GnomAD4 genome AF: 0.945 AC: 143935 AN: 152290 Hom.: 68148 Cov.: 33 AF XY: 0.944 AC XY: 70338 AN XY: 74478

African (AFR) AF: 0.881 AC: 36587 AN: 41510

American (AMR) AF: 0.970 AC: 14841 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.971 AC: 3370 AN: 3472

East Asian (EAS) AF: 0.936 AC: 4854 AN: 5186

South Asian (SAS) AF: 0.881 AC: 4255 AN: 4828

European-Finnish (FIN) AF: 0.988 AC: 10496 AN: 10624

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.976 AC: 66382 AN: 68046

Other (OTH) AF: 0.956 AC: 2023 AN: 2116

Alfa AF: 0.964 Hom.: 128043

Bravo AF: 0.943

Asia WGS AF: 0.893 AC: 3106 AN: 3478

EpiCase AF: 0.978

EpiControl AF: 0.974

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	4.4
DANN	Benign	0.85
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=89/11	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: rs410509; hg19: chr3-5241309; COSMIC: COSV108015704; COSMIC: COSV108015704;