chr1-19243990-CGT-GCG

Variant names:

• chr1-19243990-CGT-GCG
• NM_015047.3:c.244_246delACGinsCGC
• EMC1 p.Thr82Arg

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM5

The NM_015047.3(EMC1):​c.244_246delACGinsCGC​(p.Thr82Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T82M) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EMC1 NM_015047.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.93
• Publications: 0 publications found

Genes affected

EMC1 (HGNC:28957): (ER membrane protein complex subunit 1) This gene encodes a single-pass type I transmembrane protein, which is a subunit of the endoplasmic reticulum membrane protein complex (EMC). Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2012]

EMC1 Gene-Disease associations (from GenCC):

• cerebellar atrophy, visual impairment, and psychomotor retardation;

  Inheritance: AR, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• complex neurodevelopmental disorder with motor features

  Inheritance: AD, AR Classification: MODERATE Submitted by: ClinGen
• global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr1-19243991-G-A is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 219100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015047.3. 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
	EMC1	NM_015047.3	MANE Select	c.244_246delACGinsCGC	p.Thr82Arg	missense	N/A	NP_055862.1	Q8N766-1
	EMC1	NM_001375820.1		c.244_246delACGinsCGC	p.Thr82Arg	missense	N/A	NP_001362749.1	H7C5A2
	EMC1	NM_001375821.1		c.244_246delACGinsCGC	p.Thr82Arg	missense	N/A	NP_001362750.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMC1	ENST00000477853.6	TSL:1 MANE Select	c.244_246delACGinsCGC	p.Thr82Arg	missense	N/A	ENSP00000420608.1	Q8N766-1
	EMC1	ENST00000375199.7	TSL:1	c.244_246delACGinsCGC	p.Thr82Arg	missense	N/A	ENSP00000364345.3	Q8N766-2
	EMC1	ENST00000911107.1		c.244_246delACGinsCGC	p.Thr82Arg	missense	N/A	ENSP00000581166.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-19570484;