Variant 22-39511970-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019008.6(MIEF1):c.266C>T(p.Thr89Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00511 in 1,614,126 control chromosomes in the GnomAD database, including 357 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.026 ( 183 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 174 hom. )

Consequence

MIEF1
NM_019008.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.62

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018825829).

BP6

Variant 22-39511970-C-T is Benign according to our data. Variant chr22-39511970-C-T is described in ClinVar as [Benign]. Clinvar id is 783887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIEF1	NM_019008.6 link	c.266C>T	p.Thr89Met	missense_variant	4/6	ENST00000325301.7	NP_061881.2	Q9NQG6-1A0A024R1L3
MIEF1	NM_001304564.2 link	c.266C>T	p.Thr89Met	missense_variant	4/7		NP_001291493.1	Q9NQG6B0QY95Q9H0J7
MIEF1	NR_130789.2 link	n.753C>T		non_coding_transcript_exon_variant	4/6
MIEF1	NR_130790.2 link	n.903C>T		non_coding_transcript_exon_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIEF1	ENST00000325301.7 link	c.266C>T	p.Thr89Met	missense_variant	4/6	1	NM_019008.6	ENSP00000327124.2		Q9NQG6-1

Frequencies

GnomAD3 genomes

AF:

0.0260

AC:

3959

AN:

152210

Hom.:

182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0904

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00955

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0181

GnomAD3 exomes

AF:

0.00705

AC:

1772

AN:

251274

Hom.:

AF XY:

0.00500

AC XY:

679

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.0953

Gnomad AMR exome

AF:

0.00434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000369

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00293

AC:

4290

AN:

1461798

Hom.:

174

Cov.:

AF XY:

0.00258

AC XY:

1873

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0947

Gnomad4 AMR exome

AF:

0.00496

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000398

Gnomad4 OTH exome

AF:

0.00649

GnomAD4 genome

AF:

0.0260

AC:

3964

AN:

152328

Hom.:

183

Cov.:

AF XY:

0.0255

AC XY:

1898

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0903

Gnomad4 AMR

AF:

0.00954

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.00474

Hom.:

Bravo

AF:

0.0294

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0817

AC:

360

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00872

AC:

1059

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

T;T;T

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

D;.;D

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

.;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.079

Sift

Benign

0.067

T;T;T

Sift4G

Benign

0.077

T;T;T

Polyphen

0.71

P;P;P

Vest4

0.17

MVP

0.43

MPC

0.35

ClinPred

0.018

GERP RS

4.8

Varity_R

0.053

gMVP

0.18

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