Variant 17-18263436-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_139162.4(MIEF2):c.310+188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000806 in 942,698 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00043 ( 1 hom. )

Consequence

MIEF2
NM_139162.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.149

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant 17-18263436-G-A is Benign according to our data. Variant chr17-18263436-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2647550.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MIEF2	NM_139162.4 linkuse as main transcript	c.310+188G>A	intron_variant	ENST00000323019.9	NP_631901.2	Q96C03-1
MIEF2	NM_148886.2 linkuse as main transcript	c.343+188G>A	intron_variant		NP_683684.2	Q96C03-3
MIEF2	NM_001144900.3 linkuse as main transcript	c.310+188G>A	intron_variant		NP_001138372.1	Q96C03-2
MIEF2	XM_017024190.2 linkuse as main transcript	c.331+188G>A	intron_variant		XP_016879679.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIEF2	ENST00000323019.9 linkuse as main transcript	c.310+188G>A		intron_variant		2	NM_139162.4	ENSP00000323591.4		Q96C03-1

Frequencies

GnomAD3 genomes

AF:

0.00272

AC:

413

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00930

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000689

AC:

100

AN:

145146

Hom.:

AF XY:

0.000575

AC XY:

AN XY:

78282

show subpopulations

Gnomad AFR exome

AF:

0.00941

Gnomad AMR exome

AF:

0.000810

Gnomad ASJ exome

AF:

0.000120

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000436

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000147

Gnomad OTH exome

AF:

0.000702

GnomAD4 exome

AF:

0.000431

AC:

341

AN:

790476

Hom.:

Cov.:

AF XY:

0.000347

AC XY:

143

AN XY:

411864

show subpopulations

Gnomad4 AFR exome

AF:

0.00982

Gnomad4 AMR exome

AF:

0.000717

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000148

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000129

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

AF:

0.00275

AC:

419

AN:

152222

Hom.:

Cov.:

AF XY:

0.00270

AC XY:

201

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00941

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.00311

ExAC

AF:

0.000370

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

MIEF2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.80

FATHMM_MKL

Benign

0.062

M_CAP

Benign

0.0018

MetaRNN

Benign

0.0043

Vest4

0.077

MVP

0.53

GERP RS

1.4

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: -20

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