rs35693261

Positions:

• chr20-62200866-C-A
• chr20-62200866-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A337V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• 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 Uncertain_significance. Variant got 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/exons	MANE	Protein	UniProt
MTG2	NM_015666.4	c.1010C>A	p.Ala337Glu	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	c.1010C>A	p.Ala337Glu	missense_variant	7/7	5	NM_015666.4	ENSP00000359859	P1
MTG2	ENST00000467101.5	c.*474C>A		3_prime_UTR_variant, NMD_transcript_variant	6/6	1		ENSP00000435214

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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
MutationTaster	Benign	1.0	N;N;N
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

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;