chr20-62197870-C-T

Variant names:

• chr20-62197870-C-T
• rs1177126463
• NM_015666.4:c.371C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015666.4(MTG2):​c.371C>T​(p.Ser124Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MTG2 NM_015666.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.20
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.882

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.371C>T	p.Ser124Phe	missense	Exon 4 of 7	NP_056481.1	Q9H4K7-1
	MTG2	NM_001384347.1		c.425C>T	p.Ser142Phe	missense	Exon 4 of 7	NP_001371276.1
	MTG2	NM_001384348.1		c.371C>T	p.Ser124Phe	missense	Exon 4 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.371C>T	p.Ser124Phe	missense	Exon 4 of 7	ENSP00000359859.3	Q9H4K7-1
	MTG2	ENST00000467101.5	TSL:1	n.353-764C>T		intron	N/A	ENSP00000435214.1	B4DRC1
	MTG2	ENST00000948274.1		c.425C>T	p.Ser142Phe	missense	Exon 4 of 7	ENSP00000618333.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461866 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.078	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.45	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		6.2
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.67		Loss of disorder (P = 0.0037)
MVP		0.74
MPC		0.84
ClinPred		1.0	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.57
gMVP		0.78
Mutation Taster		=28/72	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1177126463; hg19: chr20-60772926;