Variant 17-18262758-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_139162.4(MIEF2):c.38G>T(p.Ser13Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000824 in 1,455,832 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000082 ( 1 hom. )

Consequence

MIEF2
NM_139162.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.732

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 2 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity MID49_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07268527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIEF2	NM_139162.4 linkuse as main transcript	c.38G>T	p.Ser13Ile	missense_variant	2/4	ENST00000323019.9	NP_631901.2	Q96C03-1
MIEF2	NM_148886.2 linkuse as main transcript	c.71G>T	p.Ser24Ile	missense_variant	2/4		NP_683684.2	Q96C03-3
MIEF2	NM_001144900.3 linkuse as main transcript	c.38G>T	p.Ser13Ile	missense_variant	2/4		NP_001138372.1	Q96C03-2
MIEF2	XM_017024190.2 linkuse as main transcript	c.59G>T	p.Ser20Ile	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.38G>T	p.Ser13Ile	missense_variant	2/4	2	NM_139162.4	ENSP00000323591.4		Q96C03-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000407

AC:

AN:

245818

Hom.:

AF XY:

0.00000750

AC XY:

AN XY:

133368

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:

0.0000333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000824

AC:

AN:

1455832

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

723800

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000584

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000825

AC:

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

Apr 25, 2022

The c.71G>T (p.S24I) alteration is located in exon 2 (coding exon 2) of the MIEF2 gene. This alteration results from a G to T substitution at nucleotide position 71, causing the serine (S) at amino acid position 24 to be replaced by an isoleucine (I). 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

Benign

-0.33

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

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

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.27

M_CAP

Benign

0.0071

MetaRNN

Benign

0.073

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.;N;.;.;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.7

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

REVEL

Benign

0.037

Sift

Uncertain

0.0050

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

Sift4G

Uncertain

0.0090

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

Polyphen

0.0

B;.;B;B;.;.;.

Vest4

0.17

MutPred

0.26

Loss of phosphorylation at S13 (P = 0.0039);Loss of phosphorylation at S13 (P = 0.0039);Loss of phosphorylation at S13 (P = 0.0039);Loss of phosphorylation at S13 (P = 0.0039);Loss of phosphorylation at S13 (P = 0.0039);Loss of phosphorylation at S13 (P = 0.0039);.;

MVP

0.16

MPC

0.38

ClinPred

0.089

GERP RS

1.9

Varity_R

0.097

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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