Variant 22-39513842-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_019008.6(MIEF1):c.911G>A(p.Arg304His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00515 in 1,614,054 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 30 hom. )

Consequence

MIEF1
NM_019008.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.17

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036183596).

BP6

Variant 22-39513842-G-A is Benign according to our data. Variant chr22-39513842-G-A is described in ClinVar as [Benign]. Clinvar id is 787193.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 669 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MIEF1	NM_019008.6 linkuse as main transcript	c.911G>A	p.Arg304His	missense_variant	6/6	ENST00000325301.7
MIEF1	NM_001304564.2 linkuse as main transcript	c.911G>A	p.Arg304His	missense_variant	6/7
MIEF1	NR_130789.2 linkuse as main transcript	n.1312G>A		non_coding_transcript_exon_variant	6/6
MIEF1	NR_130790.2 linkuse as main transcript	n.1462G>A		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIEF1	ENST00000325301.7 linkuse as main transcript	c.911G>A	p.Arg304His	missense_variant	6/6	1	NM_019008.6	P1	Q9NQG6-1

Frequencies

GnomAD3 genomes

AF:

0.00440

AC:

669

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.0192

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00547

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00522

AC:

1313

AN:

251312

Hom.:

AF XY:

0.00547

AC XY:

743

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.000862

Gnomad AMR exome

AF:

0.00208

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.0220

Gnomad NFE exome

AF:

0.00554

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00523

AC:

7641

AN:

1461782

Hom.:

Cov.:

AF XY:

0.00511

AC XY:

3715

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.00199

Gnomad4 ASJ exome

AF:

0.00145

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00226

Gnomad4 FIN exome

AF:

0.0217

Gnomad4 NFE exome

AF:

0.00517

Gnomad4 OTH exome

AF:

0.00603

GnomAD4 genome

AF:

0.00439

AC:

668

AN:

152272

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

379

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.0192

Gnomad4 NFE

AF:

0.00547

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00392

Hom.:

Bravo

AF:

0.00299

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00465

AC:

ExAC

AF:

0.00507

AC:

616

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00431

EpiControl

AF:

0.00445

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 11, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.011

T;T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.091

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.84

T;.;T

MetaRNN

Benign

0.0036

T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.47

N;N;N

REVEL

Benign

0.063

Sift

Benign

0.27

T;T;T

Sift4G

Benign

0.15

T;T;T

Polyphen

0.83

P;P;P

Vest4

0.16

MVP

0.31

MPC

0.52

ClinPred

0.014

GERP RS

0.34

Varity_R

0.18

gMVP

0.25

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