chr1-19219327-C-T

Variant names:

• chr1-19219327-C-T
• NM_015047.3:c.2958G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4 BP6_Moderate BP7

The NM_015047.3(EMC1):​c.2958G>A​(p.Lys986Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: EMC1 NM_015047.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0840
• 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-AS1 (HGNC:54050): (EMC1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.234).
• BP6: Variant 1-19219327-C-T is Benign according to our data. Variant chr1-19219327-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2974133.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.084 with no splicing effect.

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.2958G>A	p.Lys986Lys	synonymous	Exon 23 of 23	NP_055862.1	Q8N766-1
	EMC1	NM_001375820.1		c.2967G>A	p.Lys989Lys	synonymous	Exon 24 of 24	NP_001362749.1	H7C5A2
	EMC1	NM_001375821.1		c.2964G>A	p.Lys988Lys	synonymous	Exon 24 of 24	NP_001362750.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMC1	ENST00000477853.6	TSL:1 MANE Select	c.2958G>A	p.Lys986Lys	synonymous	Exon 23 of 23	ENSP00000420608.1	Q8N766-1
	EMC1	ENST00000375199.7	TSL:1	c.2955G>A	p.Lys985Lys	synonymous	Exon 23 of 23	ENSP00000364345.3	Q8N766-2
	EMC1	ENST00000911107.1		c.3033G>A	p.Lys1011Lys	synonymous	Exon 24 of 24	ENSP00000581166.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	3.2
DANN	Benign	0.83
PhyloP100		-0.084
Mutation Taster		=96/4	polymorphism

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

hg19: chr1-19545821; COSMIC: COSV64345715; COSMIC: COSV64345715;