10-133394314-C-T

Variant names:

• chr10-133394314-C-T
• rs1372152083
• NM_138384.4:c.94C>T

Variant summary

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

The NM_138384.4(MTG1):​c.94C>T​(p.Pro32Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000213 in 1,362,798 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: MTG1 NM_138384.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21

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.94C>T	p.Pro32Ser	missense_variant	Exon 1 of 11	ENST00000317502.11	NP_612393.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTG1	ENST00000317502.11	c.94C>T	p.Pro32Ser	missense_variant	Exon 1 of 11	1	NM_138384.4	ENSP00000323047.6
MTG1	ENST00000477902.6	c.-12+130C>T		intron_variant	Intron 1 of 10	3		ENSP00000475596.1
ENSG00000254536	ENST00000468317.3	n.*37-1399C>T		intron_variant	Intron 6 of 15	5		ENSP00000436767.2
ENSG00000254536	ENST00000670407.1	n.*279-1399C>T		intron_variant	Intron 5 of 6			ENSP00000499264.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.0000213 AC: 29 AN: 1362798 Hom.: 0 Cov.: 31 AF XY: 0.0000238 AC XY: 16 AN XY: 672166

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000262

Gnomad4 OTH exome AF: 0.0000176

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.94C>T (p.P32S) alteration is located in exon 1 (coding exon 1) of the MTG1 gene. This alteration results from a C to T substitution at nucleotide position 94, causing the proline (P) at amino acid position 32 to be replaced by a serine (S). 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	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Uncertain	-0.049	T
MutationAssessor	Pathogenic	4.0	H;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.9	D;D
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	D;.
Vest4		0.44
MutPred		0.76		Loss of loop (P = 0.0512);Loss of loop (P = 0.0512);
MVP		0.84
MPC		0.17
ClinPred		1.0	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.88
gMVP		0.60

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

LitVar

Other links and lift over

dbSNP: rs1372152083; hg19: chr10-135207818;