Genetic Variant MIEF1:c.*3092C>T (chr22-39517415-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_019008.6(MIEF1):c.*3092C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 315,248 control chromosomes in the GnomAD database, including 13,389 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 0.30 ( 6853 hom., cov: 32)

Exomes 𝑓: 0.27 ( 6536 hom. )

Consequence

MIEF1
NM_019008.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.80

Publications

14 publications found

Variant links:

Genes affected

MIEF1 (HGNC:25979): (mitochondrial elongation factor 1) Enables ADP binding activity; GDP binding activity; and identical protein binding activity. Involved in several processes, including positive regulation of mitochondrial fission; positive regulation of mitochondrial translation; and positive regulation of protein targeting to membrane. Located in mitochondrial matrix and mitochondrial outer membrane. Colocalizes with mitochondrial large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

MIEF1 Gene-Disease associations (from GenCC):

optic atrophy 14
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

MIEF1 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=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MIEF1	NM_019008.6 link	c.*3092C>T	3_prime_UTR_variant	Exon 6 of 6	ENST00000325301.7	NP_061881.2	Q9NQG6-1A0A024R1L3
MIEF1	NR_130789.2 link	n.4885C>T	non_coding_transcript_exon_variant	Exon 6 of 6
MIEF1	NR_130790.2 link	n.5035C>T	non_coding_transcript_exon_variant	Exon 7 of 7
MIEF1	NM_001304564.2 link	c.*2042C>T	3_prime_UTR_variant	Exon 7 of 7		NP_001291493.1	Q9NQG6B0QY95Q9H0J7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIEF1	ENST00000325301.7 link	c.*3092C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_019008.6	ENSP00000327124.2		Q9NQG6-1

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45198

AN:

151930

Hom.:

6858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.282

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.331

Gnomad FIN

AF:

0.332

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.304

GnomAD4 exome

AF:

0.273

AC:

44617

AN:

163200

Hom.:

6536

Cov.:

AF XY:

0.279

AC XY:

25481

AN XY:

91434

show subpopulations

African (AFR)

AF:

0.205

AC:

698

AN:

3398

American (AMR)

AF:

0.227

AC:

1784

AN:

7850

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

1082

AN:

3848

East Asian (EAS)

AF:

0.140

AC:

692

AN:

4946

South Asian (SAS)

AF:

0.296

AC:

10151

AN:

34278

European-Finnish (FIN)

AF:

0.306

AC:

6207

AN:

20294

Middle Eastern (MID)

AF:

0.289

AC:

187

AN:

648

European-Non Finnish (NFE)

AF:

0.272

AC:

21927

AN:

80716

Other (OTH)

AF:

0.262

AC:

1889

AN:

7222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

1401

2802

4203

5604

7005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

122

244

366

488

610

<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:

0.297

AC:

45205

AN:

152048

Hom.:

6853

Cov.:

AF XY:

0.296

AC XY:

22026

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.274

AC:

11366

AN:

41456

American (AMR)

AF:

0.281

AC:

4301

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

1188

AN:

3472

East Asian (EAS)

AF:

0.176

AC:

915

AN:

5186

South Asian (SAS)

AF:

0.330

AC:

1593

AN:

4822

European-Finnish (FIN)

AF:

0.332

AC:

3500

AN:

10544

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.313

AC:

21291

AN:

67970

Other (OTH)

AF:

0.302

AC:

637

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1661

3323

4984

6646

8307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

476

952

1428

1904

2380

<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:

0.310

Hom.:

28349

Bravo

AF:

0.292

Asia WGS

AF:

0.314

AC:

1095

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.26

(source)

DANN

Benign

0.65

PhyloP100

-1.8

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