Genetic Variant MIEF1:p.Asp264Asn (chr22-39513721-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_019008.6(MIEF1):c.790G>A(p.Asp264Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00875 in 1,614,212 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0062 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 89 hom. )

Consequence

MIEF1
NM_019008.6 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 9.99

Publications

7 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066976547).

BS2

High AC in GnomAd4 at 941 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019008.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIEF1	NM_019008.6	MANE Select	c.790G>A	p.Asp264Asn	missense	Exon 6 of 6	NP_061881.2
MIEF1	NM_001304564.2		c.790G>A	p.Asp264Asn	missense	Exon 6 of 7	NP_001291493.1	B0QY95
MIEF1	NR_130789.2		n.1191G>A		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIEF1	ENST00000325301.7	TSL:1 MANE Select	c.790G>A	p.Asp264Asn	missense	Exon 6 of 6	ENSP00000327124.2	Q9NQG6-1
MIEF1	ENST00000402881.5	TSL:1	c.790G>A	p.Asp264Asn	missense	Exon 6 of 7	ENSP00000385110.1	B0QY95
MIEF1	ENST00000433117.6	TSL:1	n.*257G>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000404096.2	Q9NQG6-2

Frequencies

GnomAD3 genomes

AF:

0.00619

AC:

943

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00443

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00594

AC:

1493

AN:

251320

AF XY:

0.00623

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00205

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00499

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00902

AC:

13190

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00882

AC XY:

6415

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

33478

American (AMR)

AF:

0.00215

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000727

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00378

AC:

326

AN:

86256

European-Finnish (FIN)

AF:

0.00490

AC:

262

AN:

53420

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0109

AC:

12069

AN:

1111996

Other (OTH)

AF:

0.00609

AC:

368

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

899

1798

2696

3595

4494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.00618

AC:

941

AN:

152342

Hom.:

Cov.:

AF XY:

0.00557

AC XY:

415

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

41576

American (AMR)

AF:

0.00411

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00456

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00443

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0106

AC:

723

AN:

68032

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

146

195

244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00871

Hom.:

Bravo

AF:

0.00607

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0106

AC:

ExAC

AF:

0.00620

AC:

753

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00938

EpiControl

AF:

0.00937

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0067

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.11

PhyloP100

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.34

Sift

Benign

0.13

Sift4G

Benign

0.20

Polyphen

0.72

Vest4

0.31

MVP

0.51

MPC

0.40

ClinPred

0.044

GERP RS

6.1

Varity_R

0.17

gMVP

0.26

Mutation Taster

=99/1

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over