Variant rs140262959 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000381120.8(MTIF3):c.413A>G(p.Gln138Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00979 in 1,614,238 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 7 hom., cov: 32)

Exomes 𝑓: 0.010 ( 88 hom. )

Consequence

MTIF3
ENST00000381120.8 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.84

Variant links:

Genes affected

MTIF3 (HGNC:29788): (mitochondrial translational initiation factor 3) This gene encodes a translation initiation factor that is involved in mitochondrial protein synthesis. Polymorphism in this gene is associated with the onset of Parkinson's disease. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 5. [provided by RefSeq, Oct 2009]

MTIF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007491678).

BP6

Variant 13-27440036-T-C is Benign according to our data. Variant chr13-27440036-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 445609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-27440036-T-C is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTIF3	NM_152912.5 linkuse as main transcript	c.413A>G	p.Gln138Arg	missense_variant	3/5	ENST00000381120.8	NP_690876.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTIF3	ENST00000381120.8 linkuse as main transcript	c.413A>G	p.Gln138Arg	missense_variant	3/5	1	NM_152912.5	ENSP00000370512	P1

Frequencies

GnomAD3 genomes

AF:

0.00725

AC:

1103

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00556

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0126

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00772

AC:

1941

AN:

251482

Hom.:

AF XY:

0.00801

AC XY:

1089

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00460

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.0114

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.00929

GnomAD4 exome

AF:

0.0101

AC:

14706

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

7269

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00478

Gnomad4 ASJ exome

AF:

0.00409

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000974

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.0119

Gnomad4 OTH exome

AF:

0.00791

GnomAD4 genome

AF:

0.00723

AC:

1102

AN:

152346

Hom.:

Cov.:

AF XY:

0.00701

AC XY:

522

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00238

Gnomad4 AMR

AF:

0.00556

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0126

Gnomad4 NFE

AF:

0.0110

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.0101

Hom.:

Bravo

AF:

0.00695

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.0117

AC:

101

ExAC

AF:

0.00814

AC:

988

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.0117

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 15, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.038

T;T;T

Eigen

Benign

0.069

Eigen_PC

Benign

0.067

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.63

.;.;T

MetaRNN

Benign

0.0075

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.3

M;M;M

MutationTaster

Benign

0.61

D;D;D;D

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0090

D;D;D

Sift4G

Uncertain

0.011

D;D;D

Polyphen

0.67

P;P;P

Vest4

0.14

MVP

0.46

MPC

0.36

ClinPred

0.017

GERP RS

6.0

Varity_R

0.14

gMVP

0.38

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