16-85779920-G-T

Variant names:

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

Variant summary

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

The NM_006067.5(EMC8):​c.474-53C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000777 in 1,415,774 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000078 (0 hom.)
• Consequence: EMC8 NM_006067.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• Publications: 14 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMC8	NM_006067.5	MANE Select	c.474-53C>A		intron	N/A	NP_006058.1
	EMC8	NM_001142288.2		c.379-53C>A		intron	N/A	NP_001135760.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMC8	ENST00000253457.8	TSL:1 MANE Select	c.474-53C>A		intron	N/A	ENSP00000253457.3
	EMC8	ENST00000597291.1	TSL:6	n.1304C>A		non_coding_transcript_exon	Exon 1 of 1
	EMC8	ENST00000435200.2	TSL:2	c.379-53C>A		intron	N/A	ENSP00000391730.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000777 AC: 11 AN: 1415774 Hom.: 0 Cov.: 22 AF XY: 0.00000992 AC XY: 7 AN XY: 705446

African (AFR) AF: 0.00 AC: 0 AN: 32606

American (AMR) AF: 0.00 AC: 0 AN: 43844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25742

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39206

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84582

European-Finnish (FIN) AF: 0.0000194 AC: 1 AN: 51604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4578

European-Non Finnish (NFE) AF: 0.00000744 AC: 8 AN: 1074808

Other (OTH) AF: 0.00 AC: 0 AN: 58804

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	9.7
DANN	Benign	0.66
PhyloP100		-0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: -24

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

Other links and lift over

dbSNP: rs301163; hg19: chr16-85813526;