chr20-62195850-G-T

Variant names:

• chr20-62195850-G-T
• rs372446307
• NM_015666.4:c.253G>T

Variant summary

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

The NM_015666.4(MTG2):​c.253G>T​(p.Gly85*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MTG2 NM_015666.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.33
• Publications: 2 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015666.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTG2	NM_015666.4	MANE Select	c.253G>T	p.Gly85*	stop_gained	Exon 3 of 7	NP_056481.1	Q9H4K7-1
	MTG2	NM_001384347.1		c.307G>T	p.Gly103*	stop_gained	Exon 3 of 7	NP_001371276.1
	MTG2	NM_001384348.1		c.253G>T	p.Gly85*	stop_gained	Exon 3 of 7	NP_001371277.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTG2	ENST00000370823.8	TSL:5 MANE Select	c.253G>T	p.Gly85*	stop_gained	Exon 3 of 7	ENSP00000359859.3	Q9H4K7-1
	MTG2	ENST00000467101.5	TSL:1	n.253G>T		non_coding_transcript_exon	Exon 3 of 6	ENSP00000435214.1	B4DRC1
	MTG2	ENST00000948274.1		c.307G>T	p.Gly103*	stop_gained	Exon 3 of 7	ENSP00000618333.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		7.3
Vest4		0.30
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=8/192	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs372446307; hg19: chr20-60770906;