Genetic Variant MTG1:p.Pro32Ala (chr10-133394314-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_138384.4(MTG1):c.94C>G(p.Pro32Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000734 in 1,362,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P32S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

MTG1
NM_138384.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.21

Publications

0 publications found

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]

MTG1 links:

ENSG00000254536 (HGNC:):

ENSG00000254536 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.747

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138384.4. 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
	MTG1	NM_138384.4	MANE Select	c.94C>G	p.Pro32Ala	missense	Exon 1 of 11	NP_612393.2	Q9BT17-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTG1	ENST00000317502.11	TSL:1 MANE Select	c.94C>G	p.Pro32Ala	missense	Exon 1 of 11	ENSP00000323047.6	Q9BT17-1
MTG1	ENST00000477902.6	TSL:3	c.-12+130C>G		intron	N/A	ENSP00000475596.1	U3KQ69
ENSG00000254536	ENST00000468317.3	TSL:5	n.*37-1399C>G		intron	N/A	ENSP00000436767.2	B0QZA9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000931

AC:

AN:

107374

AF XY:

0.0000168

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.34e-7

AC:

AN:

1362798

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

672166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27978

American (AMR)

AF:

0.00

AC:

AN:

33520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24202

East Asian (EAS)

AF:

0.00

AC:

AN:

31852

South Asian (SAS)

AF:

0.0000130

AC:

AN:

76898

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38752

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4924

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1067908

Other (OTH)

AF:

0.00

AC:

AN:

56764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.23

MetaRNN

Pathogenic

0.75

MetaSVM

Uncertain

-0.054

MutationAssessor

Pathogenic

3.7

PhyloP100

4.2

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.57

MutPred

0.71

Gain of catalytic residue at P32 (P = 0.0069)

MVP

0.84

MPC

0.042

ClinPred

0.99

GERP RS

4.3

PromoterAI

0.022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.84

gMVP

0.47

Mutation Taster

=41/59

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over