Genetic Variant ENSG00000259321:n.241T>C (chr14-24139938-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000558478.1(ENSG00000259321):n.241T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 488,856 control chromosomes in the GnomAD database, including 30,393 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 0.34 ( 10064 hom., cov: 32)

Exomes 𝑓: 0.32 ( 20329 hom. )

Consequence

ENSG00000259321
ENST00000558478.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.616

Publications

22 publications found

Variant links:

Genes affected

ENSG00000259321 (HGNC:):

ENSG00000259321 links:

EMC9 (HGNC:20273): (ER membrane protein complex subunit 9) 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 cytoplasm. Part of EMC complex. [provided by Alliance of Genome Resources, Apr 2022]

EMC9 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMC9	NM_016049.4 link	c.276-324A>G		intron_variant	Intron 3 of 5	ENST00000216799.9	NP_057133.2	Q9Y3B6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMC9	ENST00000216799.9 link	c.276-324A>G		intron_variant	Intron 3 of 5	1	NM_016049.4	ENSP00000216799.4		Q9Y3B6

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52136

AN:

151872

Hom.:

10059

Cov.:

show subpopulations

Gnomad AFR

AF:

0.455

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.417

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.628

Gnomad SAS

AF:

0.449

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.175

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.319

GnomAD4 exome

AF:

0.325

AC:

109390

AN:

336866

Hom.:

20329

Cov.:

AF XY:

0.330

AC XY:

62274

AN XY:

188662

show subpopulations

African (AFR)

AF:

0.457

AC:

4466

AN:

9782

American (AMR)

AF:

0.538

AC:

14639

AN:

27230

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

2494

AN:

11502

East Asian (EAS)

AF:

0.625

AC:

7166

AN:

11458

South Asian (SAS)

AF:

0.435

AC:

25505

AN:

58622

European-Finnish (FIN)

AF:

0.302

AC:

4135

AN:

13702

Middle Eastern (MID)

AF:

0.211

AC:

467

AN:

2212

European-Non Finnish (NFE)

AF:

0.245

AC:

45608

AN:

186092

Other (OTH)

AF:

0.302

AC:

4910

AN:

16266

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

3703

7406

11110

14813

18516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.343

AC:

52176

AN:

151990

Hom.:

10064

Cov.:

AF XY:

0.351

AC XY:

26067

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.455

AC:

18835

AN:

41410

American (AMR)

AF:

0.417

AC:

6368

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

690

AN:

3470

East Asian (EAS)

AF:

0.627

AC:

3248

AN:

5180

South Asian (SAS)

AF:

0.446

AC:

2152

AN:

4822

European-Finnish (FIN)

AF:

0.304

AC:

3208

AN:

10550

Middle Eastern (MID)

AF:

0.185

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.248

AC:

16828

AN:

67980

Other (OTH)

AF:

0.320

AC:

676

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1665

3330

4995

6660

8325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.334

Hom.:

6300

Bravo

AF:

0.356

Asia WGS

AF:

0.515

AC:

1789

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.6

(source)

DANN

Benign

0.77

PhyloP100

-0.62

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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