10-133395773-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_138384.4(MTG1):​c.173C>T​(p.Ala58Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,618 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: 6.8e-7 ( 0 hom. )

Consequence

MTG1
NM_138384.4 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.14
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.942

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTG1NM_138384.4 linkc.173C>T p.Ala58Val missense_variant Exon 2 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.173C>T p.Ala58Val missense_variant Exon 2 of 11 1 NM_138384.4 ENSP00000323047.6 Q9BT17-1
MTG1ENST00000477902.6 linkc.50C>T p.Ala17Val missense_variant Exon 2 of 11 3 ENSP00000475596.1 U3KQ69
ENSG00000254536ENST00000468317.3 linkn.*97C>T non_coding_transcript_exon_variant Exon 7 of 16 5 ENSP00000436767.2 B0QZA9
ENSG00000254536ENST00000670407.1 linkn.*339C>T non_coding_transcript_exon_variant Exon 6 of 7 ENSP00000499264.1 A0A590UJ37
ENSG00000254536ENST00000468317.3 linkn.*97C>T 3_prime_UTR_variant Exon 7 of 16 5 ENSP00000436767.2 B0QZA9
ENSG00000254536ENST00000670407.1 linkn.*339C>T 3_prime_UTR_variant Exon 6 of 7 ENSP00000499264.1 A0A590UJ37

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461618
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727082
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 17, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.173C>T (p.A58V) alteration is located in exon 2 (coding exon 2) of the MTG1 gene. This alteration results from a C to T substitution at nucleotide position 173, causing the alanine (A) at amino acid position 58 to be replaced by a valine (V). 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
0.84
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
.;.;T;T
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Pathogenic
0.98
.;D;D;D
M_CAP
Benign
0.0069
T
MetaRNN
Pathogenic
0.94
D;D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Pathogenic
3.3
.;.;M;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Uncertain
-3.4
D;.;D;D
REVEL
Uncertain
0.30
Sift
Uncertain
0.0020
D;.;D;D
Sift4G
Benign
0.069
T;D;D;D
Polyphen
0.64
.;.;P;.
Vest4
0.82
MutPred
0.87
.;.;Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP
0.58
MPC
0.15
ClinPred
0.98
D
GERP RS
3.3
Varity_R
0.43
gMVP
0.62

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1253195913; hg19: chr10-135209277; API