1-19242478-A-C

Variant names:

• chr1-19242478-A-C
• rs710865
• NM_015047.3:c.381-5T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015047.3(EMC1):​c.381-5T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: EMC1 NM_015047.3 splice_region, intron
• Scores: Splicing: ADA: 0.8917
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523
• Publications: 37 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: AR, AD 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).

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.381-5T>G		splice_region intron	N/A	NP_055862.1	Q8N766-1
	EMC1	NM_001375820.1		c.381-5T>G		splice_region intron	N/A	NP_001362749.1	H7C5A2
	EMC1	NM_001375821.1		c.381-5T>G		splice_region intron	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.381-5T>G		splice_region intron	N/A	ENSP00000420608.1	Q8N766-1
	EMC1	ENST00000375199.7	TSL:1	c.381-5T>G		splice_region intron	N/A	ENSP00000364345.3	Q8N766-2
	EMC1	ENST00000911107.1		c.381-5T>G		splice_region intron	N/A	ENSP00000581166.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.81
PhyloP100		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.89
dbscSNV1_RF	Benign	0.65
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.29		Position offset: -36

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

Other links and lift over

dbSNP: rs710865; hg19: chr1-19568972;