20-62193570-C-G

Position:

• chr20-62193570-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015666.4(MTG2):​c.150C>G​(p.Asp50Glu) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MTG2 NM_015666.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050745904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTG2	NM_015666.4	c.150C>G	p.Asp50Glu	missense_variant	2/7	ENST00000370823.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTG2	ENST00000370823.8	c.150C>G	p.Asp50Glu	missense_variant	2/7	5	NM_015666.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.150C>G (p.D50E) alteration is located in exon 2 (coding exon 1) of the MTG2 gene. This alteration results from a C to G substitution at nucleotide position 150, causing the aspartic acid (D) at amino acid position 50 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0027	T;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.52	N;N
REVEL	Benign	0.050
Sift	Benign	0.83	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.051	B;B
Vest4		0.18
MutPred		0.27		Gain of sheet (P = 0.0101);Gain of sheet (P = 0.0101);
MVP		0.20
MPC		0.21
ClinPred		0.16	T
GERP RS		3.2
Varity_R		0.043
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-60768626;