Variant 17-18262820-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_139162.4(MIEF2):c.100G>A(p.Val34Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000179 in 1,567,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

MIEF2
NM_139162.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.67

Variant links:

Genes affected

MIEF2 (HGNC:17920): (mitochondrial elongation factor 2) This gene encodes an outer mitochondrial membrane protein that functions in the regulation of mitochondrial morphology. It can directly recruit the fission mediator dynamin-related protein 1 (Drp1) to the mitochondrial surface. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]

MIEF2 links:

MIEF2 (HGNC:):

MIEF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33878356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIEF2	NM_139162.4 linkuse as main transcript	c.100G>A	p.Val34Met	missense_variant	2/4	ENST00000323019.9	NP_631901.2	Q96C03-1
MIEF2	NM_148886.2 linkuse as main transcript	c.133G>A	p.Val45Met	missense_variant	2/4		NP_683684.2	Q96C03-3
MIEF2	NM_001144900.3 linkuse as main transcript	c.100G>A	p.Val34Met	missense_variant	2/4		NP_001138372.1	Q96C03-2
MIEF2	XM_017024190.2 linkuse as main transcript	c.121G>A	p.Val41Met	missense_variant	2/4		XP_016879679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIEF2	ENST00000323019.9 linkuse as main transcript	c.100G>A	p.Val34Met	missense_variant	2/4	2	NM_139162.4	ENSP00000323591.4		Q96C03-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000142

AC:

AN:

211024

Hom.:

AF XY:

0.0000176

AC XY:

AN XY:

113608

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000515

Gnomad NFE exome

AF:

0.0000209

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000177

AC:

AN:

1415336

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

699026

show subpopulations

Gnomad4 AFR exome

AF:

0.0000312

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.0000588

Gnomad4 NFE exome

AF:

0.0000147

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 17, 2023

The c.133G>A (p.V45M) alteration is located in exon 2 (coding exon 2) of the MIEF2 gene. This alteration results from a G to A substitution at nucleotide position 133, causing the valine (V) at amino acid position 45 to be replaced by a methionine (M). 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

0.20

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

T;.;.;T;T;T;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.94

M_CAP

Benign

0.0069

MetaRNN

Benign

0.34

T;T;T;T;T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.5

M;.;M;.;.;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.4

N;.;D;D;.;.;N

REVEL

Benign

0.26

Sift

Uncertain

0.0020

D;.;D;D;.;.;D

Sift4G

Uncertain

0.0050

D;D;D;D;D;D;D

Polyphen

0.98

D;.;D;D;.;.;.

Vest4

0.33

MVP

0.68

MPC

0.52

ClinPred

0.47

GERP RS

3.3

Varity_R

0.14

gMVP

0.69

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