chr16-85779625-A-C

Position:

• chr16-85779625-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006067.5(EMC8):​c.*83T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 1,409,332 control chromosomes in the GnomAD database, including 403,836 homozygotes. 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: 𝑓 0.68 (36760 hom., cov: 32)
  • Exomes 𝑓: 0.75 (367076 hom.)
• Consequence: EMC8 NM_006067.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMC8	NM_006067.5	c.*83T>G		3_prime_UTR_variant	5/5	ENST00000253457.8	NP_006058.1
EMC8	NM_001142288.2	c.*240T>G		3_prime_UTR_variant	4/4		NP_001135760.1
EMC8	XM_017022867.2	c.*83T>G		3_prime_UTR_variant	6/6		XP_016878356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMC8	ENST00000253457.8	c.*83T>G		3_prime_UTR_variant	5/5	1	NM_006067.5	ENSP00000253457	P1

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103426 AN: 151918 Hom.: 36750 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.711

GnomAD4 exome AF: 0.754 AC: 947824 AN: 1257296 Hom.: 367076 Cov.: 16 AF XY: 0.755 AC XY: 475893 AN XY: 630706

Gnomad4 AFR exome AF: 0.541

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.718

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.691

Gnomad4 FIN exome AF: 0.822

Gnomad4 NFE exome AF: 0.798

Gnomad4 OTH exome AF: 0.728

GnomAD4 genome AF: 0.681 AC: 103468 AN: 152036 Hom.: 36760 Cov.: 32 AF XY: 0.678 AC XY: 50383 AN XY: 74354

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.792

Gnomad4 OTH AF: 0.713

Alfa AF: 0.762 Hom.: 88705

Bravo AF: 0.651

Asia WGS AF: 0.478 AC: 1662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.94
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs8587; hg19: chr16-85813231; COSMIC: COSV53668474; COSMIC: COSV53668474;