20-62195940-A-C

Position:

• chr20-62195940-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015666.4(MTG2):​c.343A>C​(p.Ile115Leu) 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. 14/21 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: 2.62

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=0.24130124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTG2	NM_015666.4	c.343A>C	p.Ile115Leu	missense_variant	3/7	ENST00000370823.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTG2	ENST00000370823.8	c.343A>C	p.Ile115Leu	missense_variant	3/7	5	NM_015666.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

May 10, 2022

The c.343A>C (p.I115L) alteration is located in exon 3 (coding exon 2) of the MTG2 gene. This alteration results from a A to C substitution at nucleotide position 343, causing the isoleucine (I) at amino acid position 115 to be replaced by a leucine (L). 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	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.013	T;.
Eigen	Benign	0.0017
Eigen_PC	Benign	0.055
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M;.
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.18
Sift	Uncertain	0.0090	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.025	B;B
Vest4		0.45
MutPred		0.65		Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);
MVP		0.31
MPC		0.26
ClinPred		0.64	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr20-60770996;