1-184708330-GA-G

Position:

• chr1-184708330-GA-G

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The ENST00000318130.13(EDEM3):​c.1859del​(p.Ile620ThrfsTer7) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EDEM3 ENST00000318130.13 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.17

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]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-184708330-GA-G is Pathogenic according to our data. Variant chr1-184708330-GA-G is described in ClinVar as [Pathogenic]. Clinvar id is 1210133.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-184708330-GA-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDEM3	NM_025191.4	c.1859del	p.Ile620ThrfsTer7	frameshift_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.1859del	p.Ile620ThrfsTer7	frameshift_variant	17/20	1	NM_025191.4	ENSP00000318147	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital disorder of glycosylation, type 2v Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-184677464;