Genetic Variant NM_006067.5:c.*83T>G (chr16-85779625-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.201

Publications

19 publications found

Variant links:

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]

EMC8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
EMC8	NM_006067.5 link	c.*83T>G	3_prime_UTR_variant	Exon 5 of 5	ENST00000253457.8	NP_006058.1	O43402-1Q53Y03
EMC8	NM_001142288.2 link	c.*240T>G	3_prime_UTR_variant	Exon 4 of 4		NP_001135760.1	O43402-2
EMC8	XM_017022867.2 link	c.*83T>G	3_prime_UTR_variant	Exon 6 of 6		XP_016878356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMC8	ENST00000253457.8 link	c.*83T>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_006067.5	ENSP00000253457.3		O43402-1

Frequencies

GnomAD3 genomes

AF:

0.681

AC:

103426

AN:

151918

Hom.:

36750

Cov.:

show subpopulations

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.:

AF XY:

0.755

AC XY:

475893

AN XY:

630706

show subpopulations

African (AFR)

AF:

0.541

AC:

15905

AN:

29402

American (AMR)

AF:

0.489

AC:

20838

AN:

42642

Ashkenazi Jewish (ASJ)

AF:

0.718

AC:

16854

AN:

23474

East Asian (EAS)

AF:

0.229

AC:

8768

AN:

38256

South Asian (SAS)

AF:

0.691

AC:

54721

AN:

79162

European-Finnish (FIN)

AF:

0.822

AC:

40728

AN:

49576

Middle Eastern (MID)

AF:

0.781

AC:

3870

AN:

4958

European-Non Finnish (NFE)

AF:

0.798

AC:

747263

AN:

936432

Other (OTH)

AF:

0.728

AC:

38877

AN:

53394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

10358

20716

31073

41431

51789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16434

32868

49302

65736

82170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.681

AC:

103468

AN:

152036

Hom.:

36760

Cov.:

AF XY:

0.678

AC XY:

50383

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.544

AC:

22532

AN:

41424

American (AMR)

AF:

0.578

AC:

8835

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.723

AC:

2505

AN:

3466

East Asian (EAS)

AF:

0.223

AC:

1153

AN:

5160

South Asian (SAS)

AF:

0.688

AC:

3321

AN:

4824

European-Finnish (FIN)

AF:

0.828

AC:

8760

AN:

10576

Middle Eastern (MID)

AF:

0.765

AC:

225

AN:

294

European-Non Finnish (NFE)

AF:

0.792

AC:

53856

AN:

67980

Other (OTH)

AF:

0.713

AC:

1508

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1564

3129

4693

6258

7822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.746

Hom.:

135904

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

(source)

DANN

Benign

0.65

PhyloP100

-0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over