10-133399219-G-C

Variant names:

• chr10-133399219-G-C
• NM_138384.4:c.413G>C

Variant summary

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

The NM_138384.4(MTG1):​c.413G>C​(p.Arg138Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTG1 NM_138384.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.76

Genes affected

MTG1 (HGNC:32159): (mitochondrial ribosome associated GTPase 1) Enables GTPase activity. Involved in regulation of mitochondrial translation and regulation of respiratory system process. Located in mitochondrial inner membrane and mitochondrial ribosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000254536 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTG1	NM_138384.4	c.413G>C	p.Arg138Pro	missense_variant	Exon 5 of 11	ENST00000317502.11	NP_612393.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTG1	ENST00000317502.11	c.413G>C	p.Arg138Pro	missense_variant	Exon 5 of 11	1	NM_138384.4	ENSP00000323047.6
MTG1	ENST00000477902.6	c.290G>C	p.Arg97Pro	missense_variant	Exon 5 of 11	3		ENSP00000475596.1
ENSG00000254536	ENST00000468317.3	n.*337G>C		non_coding_transcript_exon_variant	Exon 10 of 16	5		ENSP00000436767.2
ENSG00000254536	ENST00000468317.3	n.*337G>C		3_prime_UTR_variant	Exon 10 of 16	5		ENSP00000436767.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.413G>C (p.R138P) alteration is located in exon 5 (coding exon 5) of the MTG1 gene. This alteration results from a G to C substitution at nucleotide position 413, causing the arginine (R) at amino acid position 138 to be replaced by a proline (P). 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	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	.;.;T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	.;D;D;T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.65	D;D;D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Pathogenic	3.2	.;.;M;.
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-6.8	D;.;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0020	D;.;D;D
Sift4G	Uncertain	0.028	D;D;D;D
Polyphen		1.0	.;.;D;D
Vest4		0.61
MutPred		0.55		.;.;Gain of glycosylation at R138 (P = 0.0351);Gain of glycosylation at R138 (P = 0.0351);
MVP		0.67
MPC		0.34
ClinPred		0.98	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.79
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr10-135212723;