22-39512414-C-T

Variant names:

Variant summary

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

The NM_019008.6(MIEF1):c.505C>T(p.Arg169Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00652 in 1,614,162 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0047 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0067 ( 41 hom. )

Consequence

MIEF1
NM_019008.6 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.12

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=0.007813871).

BP6

Variant 22-39512414-C-T is Benign according to our data. Variant chr22-39512414-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 3249210.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 718 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIEF1	NM_019008.6 link	c.505C>T	p.Arg169Trp	missense_variant	Exon 5 of 6	ENST00000325301.7	NP_061881.2	Q9NQG6-1A0A024R1L3
MIEF1	NM_001304564.2 link	c.505C>T	p.Arg169Trp	missense_variant	Exon 5 of 7		NP_001291493.1	Q9NQG6B0QY95Q9H0J7
MIEF1	NR_130789.2 link	n.906C>T		non_coding_transcript_exon_variant	Exon 5 of 6
MIEF1	NR_130790.2 link	n.1056C>T		non_coding_transcript_exon_variant	Exon 6 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIEF1	ENST00000325301.7 link	c.505C>T	p.Arg169Trp	missense_variant	Exon 5 of 6	1	NM_019008.6	ENSP00000327124.2		Q9NQG6-1

Frequencies

GnomAD3 genomes

AF:

0.00472

AC:

718

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00758

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00489

AC:

1230

AN:

251308

Hom.:

AF XY:

0.00502

AC XY:

682

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00306

Gnomad ASJ exome

AF:

0.00556

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00127

Gnomad FIN exome

AF:

0.00292

Gnomad NFE exome

AF:

0.00801

Gnomad OTH exome

AF:

0.00555

GnomAD4 exome

AF:

0.00671

AC:

9814

AN:

1461812

Hom.:

Cov.:

AF XY:

0.00649

AC XY:

4716

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00306

Gnomad4 ASJ exome

AF:

0.00582

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00108

Gnomad4 FIN exome

AF:

0.00262

Gnomad4 NFE exome

AF:

0.00795

Gnomad4 OTH exome

AF:

0.00611

GnomAD4 genome

AF:

0.00471

AC:

718

AN:

152350

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

318

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.00691

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.00758

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00683

Hom.:

Bravo

AF:

0.00459

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00930

AC:

ExAC

AF:

0.00513

AC:

623

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00867

EpiControl

AF:

0.00984

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Retinal dystrophy

Uncertain:1

Jan 01, 2022

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

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MIEF1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.065

T;T;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;.;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.0078

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.9

.;M;M

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.14

T;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

0.14

B;D;D

Vest4

0.86

MVP

0.35

MPC

1.1

ClinPred

0.041

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.64

gMVP

0.70

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