20-62200866-C-A

Variant names:

• chr20-62200866-C-A
• rs35693261
• NM_015666.4:c.1010C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015666.4(MTG2):​c.1010C>A​(p.Ala337Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 33)
• Consequence: MTG2 NM_015666.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 15 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.081746906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTG2	NM_015666.4	c.1010C>A	p.Ala337Glu	missense_variant	Exon 7 of 7	ENST00000370823.8	NP_056481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTG2	ENST00000370823.8	c.1010C>A	p.Ala337Glu	missense_variant	Exon 7 of 7	5	NM_015666.4	ENSP00000359859.3
MTG2	ENST00000467101.5	n.*474C>A		non_coding_transcript_exon_variant	Exon 6 of 6	1		ENSP00000435214.1
MTG2	ENST00000467101.5	n.*474C>A		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000435214.1
MTG2	ENST00000472005.5	n.*115C>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 344

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.16
DANN	Benign	0.27
DEOGEN2	Benign	0.00024	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.65	N
PhyloP100		1.7
PrimateAI	Benign	0.19	T
PROVEAN	Benign	2.5	N
REVEL	Benign	0.060
Sift	Benign	1.0	T
Sift4G	Benign	0.91	T
Polyphen		0.0	B
Vest4		0.088
MutPred		0.39		Gain of disorder (P = 0.031);
MVP		0.081
MPC		0.25
ClinPred		0.035	T
GERP RS		-4.4
Varity_R		0.11
gMVP		0.40
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs35693261; hg19: chr20-60775922;