Variant chr20-62200866-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MTG2	NM_015666.4 linkuse as main transcript	c.1010C>T	p.Ala337Val	missense_variant	7/7	ENST00000370823.8	NP_056481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTG2	ENST00000370823.8 linkuse as main transcript	c.1010C>T	p.Ala337Val	missense_variant	7/7	5	NM_015666.4	ENSP00000359859	P1	Q9H4K7-1
MTG2	ENST00000467101.5 linkuse as main transcript	c.*474C>T		3_prime_UTR_variant, NMD_transcript_variant	6/6	1		ENSP00000435214

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

GnomAD3 exomes

AF:

0.0331

AC:

8333

AN:

251378

Hom.:

197

AF XY:

0.0335

AC XY:

4552

AN XY:

135864

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 SAS exome

AF:

0.0105

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

Gnomad4 AFR exome

AF:

0.00708

Gnomad4 AMR exome

AF:

0.0248

Gnomad4 ASJ exome

AF:

0.0351

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0105

Gnomad4 FIN exome

AF:

0.0337

Gnomad4 NFE exome

AF:

0.0533

Gnomad4 OTH exome

AF:

0.0408

GnomAD4 genome

AF:

0.0319

AC:

4860

AN:

152350

Hom.:

113

Cov.:

AF XY:

0.0304

AC XY:

2265

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00947

Gnomad4 AMR

AF:

0.0282

Gnomad4 ASJ

AF:

0.0369

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00704

Gnomad4 FIN

AF:

0.0343

Gnomad4 NFE

AF:

0.0495

Gnomad4 OTH

AF:

0.0393

Alfa

AF:

0.0437

Hom.:

252

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

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

MutationTaster

Benign

1.0

N;N;N

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over