16-85779920-G-C

Variant names:

• chr16-85779920-G-C
• rs301163
• NM_006067.5:c.474-53C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006067.5(EMC8):​c.474-53C>G variant causes a 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EMC8 NM_006067.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• Publications: 0 publications found

Genes affected

EMC8 (HGNC:7864): (ER membrane protein complex subunit 8) Contributes to membrane insertase activity. Involved in protein insertion into ER membrane by stop-transfer membrane-anchor sequence and tail-anchored membrane protein insertion into ER membrane. Located in cytosol. Part of EMC complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006067.5. 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
	EMC8	NM_006067.5	MANE Select	c.474-53C>G		intron	N/A	NP_006058.1	O43402-1
	EMC8	NM_001142288.2		c.379-53C>G		intron	N/A	NP_001135760.1	O43402-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMC8	ENST00000253457.8	TSL:1 MANE Select	c.474-53C>G		intron	N/A	ENSP00000253457.3	O43402-1
	EMC8	ENST00000870912.1		c.690-53C>G		intron	N/A	ENSP00000540971.1
	EMC8	ENST00000965669.1		c.627-53C>G		intron	N/A	ENSP00000635728.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 22

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.56
PhyloP100		-0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs301163; hg19: chr16-85813526;