Genetic Variant MTIF3:p.Gln138Arg (chr13-27440036-T-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_152912.5(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. 12/21 in silico tools predict 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
NM_152912.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.84

Publications

7 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 445609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152912.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MTIF3	NM_152912.5	MANE Select	c.413A>G	p.Gln138Arg	missense	Exon 3 of 5	NP_690876.3
MTIF3	NM_001166261.2		c.413A>G	p.Gln138Arg	missense	Exon 3 of 5	NP_001159733.1
MTIF3	NM_001166262.2		c.413A>G	p.Gln138Arg	missense	Exon 3 of 5	NP_001159734.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MTIF3	ENST00000381120.8	TSL:1 MANE Select	c.413A>G	p.Gln138Arg	missense	Exon 3 of 5	ENSP00000370512.3
MTIF3	ENST00000405591.3	TSL:1	c.413A>G	p.Gln138Arg	missense	Exon 1 of 3	ENSP00000384659.2
MTIF3	ENST00000381116.5	TSL:5	c.413A>G	p.Gln138Arg	missense	Exon 5 of 7	ENSP00000370508.1

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

GnomAD2 exomes

AF:

0.00772

AC:

1941

AN:

251482

AF XY:

0.00801

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 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

African (AFR)

AF:

0.00140

AC:

AN:

33480

American (AMR)

AF:

0.00478

AC:

214

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00409

AC:

107

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000974

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0105

AC:

561

AN:

53420

Middle Eastern (MID)

AF:

0.00624

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0119

AC:

13179

AN:

1112010

Other (OTH)

AF:

0.00791

AC:

478

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

897

1793

2690

3586

4483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

500

1000

1500

2000

2500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00723

AC:

1102

AN:

152346

Hom.:

Cov.:

AF XY:

0.00701

AC XY:

522

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00238

AC:

AN:

41596

American (AMR)

AF:

0.00556

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0126

AC:

134

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0110

AC:

746

AN:

68024

Other (OTH)

AF:

0.00992

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

116

174

232

290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00978

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

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.038

Eigen

Benign

0.069

Eigen_PC

Benign

0.067

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0075

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.3

PhyloP100

5.8

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.6

REVEL

Benign

0.14

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.011

Polyphen

0.67

Vest4

0.14

MVP

0.46

MPC

0.36

ClinPred

0.017

GERP RS

6.0

PromoterAI

-0.013

Neutral

(source)

Varity_R

0.14

gMVP

0.38

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over