Variant 22-39513721-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000325301.7(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 Lovd as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0062 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 89 hom. )

Consequence

MIEF1
ENST00000325301.7 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 9.99

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

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

BP6

Variant 22-39513721-G-A is Benign according to our data. Variant chr22-39513721-G-A is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 941 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MIEF1	NM_019008.6 linkuse as main transcript	c.790G>A	p.Asp264Asn	missense_variant	6/6	ENST00000325301.7	NP_061881.2
MIEF1	NM_001304564.2 linkuse as main transcript	c.790G>A	p.Asp264Asn	missense_variant	6/7		NP_001291493.1
MIEF1	NR_130789.2 linkuse as main transcript	n.1191G>A		non_coding_transcript_exon_variant	6/6
MIEF1	NR_130790.2 linkuse as main transcript	n.1341G>A		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIEF1	ENST00000325301.7 linkuse as main transcript	c.790G>A	p.Asp264Asn	missense_variant	6/6	1	NM_019008.6	ENSP00000327124	P1	Q9NQG6-1

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

GnomAD3 exomes

AF:

0.00594

AC:

1493

AN:

251320

Hom.:

AF XY:

0.00623

AC XY:

846

AN XY:

135856

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 SAS exome

AF:

0.00369

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

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.000727

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00378

Gnomad4 FIN exome

AF:

0.00490

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.00609

GnomAD4 genome

AF:

0.00618

AC:

941

AN:

152342

Hom.:

Cov.:

AF XY:

0.00557

AC XY:

415

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00411

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.00443

Gnomad4 NFE

AF:

0.0106

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00913

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Retinal dystrophy

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Jan 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

T;T;T

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.71

T;.;T

MetaRNN

Benign

0.0067

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.11

.;N;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.1

N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.72

P;B;B

Vest4

0.31

MVP

0.51

MPC

0.40

ClinPred

0.044

GERP RS

6.1

Varity_R

0.17

gMVP

0.26

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over