NM_015047.3(EMC1):c.2059C>T (p.Arg687Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 18, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000760591.9

Allele description [Variation Report for NM_015047.3(EMC1):c.2059C>T (p.Arg687Ter)]

NM_015047.3(EMC1):c.2059C>T (p.Arg687Ter)

Genes:

EMC1-AS1:EMC1 antisense RNA 1 [Gene - HGNC]
EMC1:ER membrane protein complex subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.13

Genomic location:

Preferred name:

NM_015047.3(EMC1):c.2059C>T (p.Arg687Ter)

HGVS:

NC_000001.11:g.19230849G>A
NG_032948.1:g.25711C>T
NM_001271427.2:c.2056C>T
NM_001271428.2:c.2056C>T
NM_001271429.2:c.1993C>T
NM_015047.3:c.2059C>TMANE SELECT
NP_001258356.1:p.Arg686Ter
NP_001258357.1:p.Arg686Ter
NP_001258358.1:p.Arg665Ter
NP_055862.1:p.Arg687Ter
NC_000001.10:g.19557343G>A
NM_015047.2:c.2059C>T

Protein change:

R665*

Links:

dbSNP: rs901905420

NCBI 1000 Genomes Browser:

rs901905420

Molecular consequence:

NM_001271427.2:c.2056C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001271428.2:c.2056C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001271429.2:c.1993C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_015047.3:c.2059C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000890482	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Sep 18, 2024)	germline	clinical testing	Citation Link,
SCV001198808	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 5, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 26572623, 26942288, 29271071, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000890482

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Sep 18, 2024)

germline

clinical testing

Citation Link,

SCV001198808

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 5, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Forcible destruction of severely misfolded mammalian glycoproteins by the non-glycoprotein ERAD pathway.

Ninagawa S, Okada T, Sumitomo Y, Horimoto S, Sugimoto T, Ishikawa T, Takeda S, Yamamoto T, Suzuki T, Kamiya Y, Kato K, Mori K.

J Cell Biol. 2015 Nov 23;211(4):775-84. doi: 10.1083/jcb.201504109. Epub 2015 Nov 16.

PubMed [citation]

PMID:: 26572623
PMCID:: PMC4657166

Monoallelic and Biallelic Variants in EMC1 Identified in Individuals with Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy.

Harel T, Yesil G, Bayram Y, Coban-Akdemir Z, Charng WL, Karaca E, Al Asmari A, Eldomery MK, Hunter JV, Jhangiani SN, Rosenfeld JA, Pehlivan D, El-Hattab AW, Saleh MA, LeDuc CA, Muzny D, Boerwinkle E; Baylor-Hopkins Center for Mendelian Genomics, Gibbs RA, Chung WK, Yang Y, Belmont JW, et al.

Am J Hum Genet. 2016 Mar 3;98(3):562-570. doi: 10.1016/j.ajhg.2016.01.011.

PubMed [citation]

PMID:: 26942288
PMCID:: PMC4800043

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000890482.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001198808.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 620228). This variant has not been reported in the literature in individuals affected with EMC1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Arg687*) in the EMC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in EMC1 are known to be pathogenic (PMID: 26572623, 26942288, 29271071).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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