Variant 22-39513595-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.664G>A(p.Asp222Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,614,208 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 16 hom. )

Consequence

MIEF1
NM_019008.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.00

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=0.010844678).

BP6

Variant 22-39513595-G-A is Benign according to our data. Variant chr22-39513595-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2653149.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-39513595-G-A is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd at 334 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MIEF1	NM_019008.6 linkuse as main transcript	c.664G>A	p.Asp222Asn	missense_variant	6/6	ENST00000325301.7
MIEF1	NM_001304564.2 linkuse as main transcript	c.664G>A	p.Asp222Asn	missense_variant	6/7
MIEF1	NR_130789.2 linkuse as main transcript	n.1065G>A		non_coding_transcript_exon_variant	6/6
MIEF1	NR_130790.2 linkuse as main transcript	n.1215G>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.664G>A	p.Asp222Asn	missense_variant	6/6	1	NM_019008.6	P1	Q9NQG6-1

Frequencies

GnomAD3 genomes

AF:

0.00219

AC:

334

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00340

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00257

AC:

646

AN:

251482

Hom.:

AF XY:

0.00281

AC XY:

382

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00604

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00299

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.00293

AC:

4284

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00311

AC XY:

2261

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.00471

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00632

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.00301

Gnomad4 OTH exome

AF:

0.00232

GnomAD4 genome

AF:

0.00219

AC:

334

AN:

152320

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

161

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.00189

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00393

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00340

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00307

Hom.:

Bravo

AF:

0.00210

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00302

AC:

ExAC

AF:

0.00268

AC:

326

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00398

EpiControl

AF:

0.00415

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

MIEF1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.053

T;T;T

Eigen

Uncertain

0.58

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;.;D

M_CAP

Benign

0.0040

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-1.2

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.18

Sift

Uncertain

0.0040

D;D;D

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

0.68

P;P;P

Vest4

0.65

MVP

0.61

MPC

0.52

ClinPred

0.035

GERP RS

6.1

Varity_R

0.69

gMVP

0.65

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