Variant 22-39511982-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_019008.6(MIEF1):c.278G>A(p.Arg93Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

MIEF1
NM_019008.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter 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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIEF1	NM_019008.6 link	c.278G>A	p.Arg93Gln	missense_variant	4/6	ENST00000325301.7	NP_061881.2	Q9NQG6-1A0A024R1L3
MIEF1	NM_001304564.2 link	c.278G>A	p.Arg93Gln	missense_variant	4/7		NP_001291493.1	Q9NQG6B0QY95Q9H0J7
MIEF1	NR_130789.2 link	n.765G>A		non_coding_transcript_exon_variant	4/6
MIEF1	NR_130790.2 link	n.915G>A		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.278G>A	p.Arg93Gln	missense_variant	4/6	1	NM_019008.6	ENSP00000327124.2		Q9NQG6-1

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250924

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461654

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2024

The c.278G>A (p.R93Q) alteration is located in exon 4 (coding exon 2) of the MIEF1 gene. This alteration results from a G to A substitution at nucleotide position 278, causing the arginine (R) at amino acid position 93 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0032

T;T;T

Eigen

Uncertain

0.58

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.92

D;.;D

M_CAP

Benign

0.053

MetaRNN

Uncertain

0.57

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

.;L;L

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.71

N;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.51

T;T;T

Sift4G

Benign

0.65

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.78

MutPred

0.18

Loss of MoRF binding (P = 0.0283);Loss of MoRF binding (P = 0.0283);Loss of MoRF binding (P = 0.0283);

MVP

0.55

MPC

0.79

ClinPred

0.51

GERP RS

5.9

Varity_R

0.10

gMVP

0.27

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