Genetic Variant MTG2:p.Ala337Val (chr20-62200866-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015666.4(MTG2):c.1010C>T(p.Ala337Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 1,613,978 control chromosomes in the GnomAD database, including 1,839 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.032 ( 113 hom., cov: 33)

Exomes 𝑓: 0.046 ( 1726 hom. )

Consequence

MTG2
NM_015666.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.67

Publications

15 publications found

Variant links:

Genes affected

MTG2 (HGNC:16239): (mitochondrial ribosome associated GTPase 2) Small G proteins, such as GTPBP5, act as molecular switches that play crucial roles in the regulation of fundamental cellular processes such as protein synthesis, nuclear transport, membrane trafficking, and signal transduction (Hirano et al., 2006 [PubMed 17054726]).[supplied by OMIM, Mar 2008]

MTG2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062737465).

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTG2	NM_015666.4 link	c.1010C>T	p.Ala337Val	missense_variant	Exon 7 of 7	ENST00000370823.8	NP_056481.1	Q9H4K7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MTG2	ENST00000370823.8 link	c.1010C>T	p.Ala337Val	missense_variant	Exon 7 of 7	5	NM_015666.4	ENSP00000359859.3	Q9H4K7-1
MTG2	ENST00000467101.5 link	n.*474C>T		non_coding_transcript_exon_variant	Exon 6 of 6	1		ENSP00000435214.1	B4DRC1
MTG2	ENST00000467101.5 link	n.*474C>T		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000435214.1	B4DRC1
MTG2	ENST00000472005.5 link	n.*115C>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0319

AC:

4860

AN:

152232

Hom.:

113

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00950

Gnomad AMI

AF:

0.0549

Gnomad AMR

AF:

0.0283

Gnomad ASJ

AF:

0.0369

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00703

Gnomad FIN

AF:

0.0343

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0494

Gnomad OTH

AF:

0.0397

GnomAD2 exomes

AF:

0.0331

AC:

8333

AN:

251378

AF XY:

0.0335

show subpopulations

Gnomad AFR exome

AF:

0.00960

Gnomad AMR exome

AF:

0.0232

Gnomad ASJ exome

AF:

0.0339

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0299

Gnomad NFE exome

AF:

0.0512

Gnomad OTH exome

AF:

0.0403

GnomAD4 exome

AF:

0.0457

AC:

66821

AN:

1461628

Hom.:

1726

Cov.:

AF XY:

0.0447

AC XY:

32532

AN XY:

727096

show subpopulations

African (AFR)

AF:

0.00708

AC:

237

AN:

33480

American (AMR)

AF:

0.0248

AC:

1107

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0351

AC:

917

AN:

26136

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.0105

AC:

907

AN:

86256

European-Finnish (FIN)

AF:

0.0337

AC:

1792

AN:

53172

Middle Eastern (MID)

AF:

0.0219

AC:

126

AN:

5766

European-Non Finnish (NFE)

AF:

0.0533

AC:

59266

AN:

1112004

Other (OTH)

AF:

0.0408

AC:

2464

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

3981

7962

11942

15923

19904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2150

4300

6450

8600

10750

<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:

0.0319

AC:

4860

AN:

152350

Hom.:

113

Cov.:

AF XY:

0.0304

AC XY:

2265

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00947

AC:

394

AN:

41586

American (AMR)

AF:

0.0282

AC:

432

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0369

AC:

128

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.00704

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0343

AC:

364

AN:

10622

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0495

AC:

3365

AN:

68030

Other (OTH)

AF:

0.0393

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

254

509

763

1018

1272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0438

Hom.:

344

Bravo

AF:

0.0316

TwinsUK

AF:

0.0577

AC:

214

ALSPAC

AF:

0.0537

AC:

207

ESP6500AA

AF:

0.0116

AC:

ESP6500EA

AF:

0.0517

AC:

445

ExAC

AF:

0.0335

AC:

4068

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.0484

EpiControl

AF:

0.0541

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0030

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0063

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

1.7

PrimateAI

Benign

0.19

PROVEAN

Benign

-1.3

REVEL

Benign

0.10

Sift

Benign

0.077

Sift4G

Benign

0.17

Polyphen

0.056

Vest4

0.075

MPC

0.24

ClinPred

0.013

GERP RS

-4.4

Varity_R

0.10

gMVP

0.38

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over