20-62200866-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

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]

ACMG classification

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	UniProt
MTG2	NM_015666.4	c.1010C>T	p.Ala337Val	missense_variant	7/7	ENST00000370823.8

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0319 AC: 4860 AN: 152232 Hom.: 113 Cov.: 33

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

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.: 31 AF XY: 0.0447 AC XY: 32532 AN XY: 727096

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.: 33 AF XY: 0.0304 AC XY: 2265 AN XY: 74502

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: 51

ESP6500EA AF: 0.0517 AC: 445

ExAC AF: 0.0335 AC: 4068

Asia WGS AF: 0.00462 AC: 17 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	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	12
Dann	Benign	0.92
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0063	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.10
Sift	Benign	0.077	T
Sift4G	Benign	0.17	T
Polyphen		0.056	B
Vest4		0.075
MPC		0.24
ClinPred		0.013	T
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

Other links and lift over

dbSNP: rs35693261; hg19: chr20-60775922; COSMIC: COSV63694195; COSMIC: COSV63694195;