Genetic Variant MTG1:p.Ser10Arg (chr10-133394250-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_138384.4(MTG1):c.30C>G(p.Ser10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000947 in 1,518,746 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S10G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00098 ( 7 hom. )

Consequence

MTG1
NM_138384.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.117

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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048853755).

BP6

Variant 10-133394250-C-G is Benign according to our data. Variant chr10-133394250-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2641031.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

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.30C>G	p.Ser10Arg	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.30C>G	p.Ser10Arg	missense	Exon 1 of 11	ENSP00000323047.6	Q9BT17-1
MTG1	ENST00000477902.6	TSL:3	c.-12+66C>G		intron	N/A	ENSP00000475596.1	U3KQ69
ENSG00000254536	ENST00000468317.3	TSL:5	n.*37-1463C>G		intron	N/A	ENSP00000436767.2	B0QZA9

Frequencies

GnomAD3 genomes

AF:

0.000663

AC:

101

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00202

AC:

226

AN:

111712

AF XY:

0.00265

show subpopulations

Gnomad AFR exome

AF:

0.000377

Gnomad AMR exome

AF:

0.00178

Gnomad ASJ exome

AF:

0.000138

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.00238

GnomAD4 exome

AF:

0.000978

AC:

1337

AN:

1366392

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

788

AN XY:

674200

show subpopulations

African (AFR)

AF:

0.000747

AC:

AN:

28110

American (AMR)

AF:

0.00162

AC:

AN:

33960

Ashkenazi Jewish (ASJ)

AF:

0.000165

AC:

AN:

24288

East Asian (EAS)

AF:

0.00

AC:

AN:

32350

South Asian (SAS)

AF:

0.00594

AC:

460

AN:

77382

European-Finnish (FIN)

AF:

0.0000255

AC:

AN:

39254

Middle Eastern (MID)

AF:

0.0100

AC:

AN:

4200

European-Non Finnish (NFE)

AF:

0.000647

AC:

692

AN:

1069966

Other (OTH)

AF:

0.00109

AC:

AN:

56882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

148

221

295

369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<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

AF:

0.000663

AC:

101

AN:

152354

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.000216

AC:

AN:

41594

American (AMR)

AF:

0.00105

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00393

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000720

AC:

AN:

68028

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000618

Hom.:

Bravo

AF:

0.000657

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.00114

AC:

Asia WGS

AF:

0.00116

AC:

AN:

3470

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.029

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.43

M_CAP

Benign

0.0099

MetaRNN

Benign

0.0049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

-0.12

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.56

REVEL

Benign

0.094

Sift

Benign

0.35

Sift4G

Benign

0.27

Polyphen

0.69

Vest4

0.13

MutPred

0.55

Gain of MoRF binding (P = 0.0119)

MVP

0.35

MPC

0.025

ClinPred

0.027

GERP RS

-0.65

PromoterAI

0.15

Neutral

(source)

Varity_R

0.075

gMVP

0.30

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over