10-133394282-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138384.4(MTG1):​c.62C>A​(p.Pro21His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000513 in 1,365,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

MTG1
NM_138384.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.15
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.18085402).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTG1NM_138384.4 linkc.62C>A p.Pro21His missense_variant Exon 1 of 11 ENST00000317502.11 NP_612393.2 Q9BT17-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTG1ENST00000317502.11 linkc.62C>A p.Pro21His missense_variant Exon 1 of 11 1 NM_138384.4 ENSP00000323047.6 Q9BT17-1
MTG1ENST00000477902.6 linkc.-12+98C>A intron_variant Intron 1 of 10 3 ENSP00000475596.1 U3KQ69
ENSG00000254536ENST00000468317.3 linkn.*37-1431C>A intron_variant Intron 6 of 15 5 ENSP00000436767.2 B0QZA9
ENSG00000254536ENST00000670407.1 linkn.*279-1431C>A intron_variant Intron 5 of 6 ENSP00000499264.1 A0A590UJ37

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000513
AC:
7
AN:
1365220
Hom.:
0
Cov.:
31
AF XY:
0.00000297
AC XY:
2
AN XY:
673500
show subpopulations
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:
0.00000655
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 09, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.62C>A (p.P21H) alteration is located in exon 1 (coding exon 1) of the MTG1 gene. This alteration results from a C to A substitution at nucleotide position 62, causing the proline (P) at amino acid position 21 to be replaced by a histidine (H). 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
0.12
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
18
DANN
Benign
0.96
DEOGEN2
Benign
0.075
T;T
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.62
FATHMM_MKL
Benign
0.43
N
LIST_S2
Benign
0.55
T;T
M_CAP
Benign
0.025
T
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.3
M;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-1.2
N;N
REVEL
Benign
0.10
Sift
Benign
0.14
T;T
Sift4G
Benign
0.12
T;T
Polyphen
0.39
B;.
Vest4
0.31
MutPred
0.47
Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP
0.45
MPC
0.049
ClinPred
0.49
T
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.053
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: chr10-135207786; API