Genetic Variant NM_138384.4:c.16C>A (chr10-133394236-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138384.4(MTG1):c.16C>A(p.Arg6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000733 in 1,364,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. R6C) 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: 1.86

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.124673724).

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.16C>A	p.Arg6Ser	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.16C>A	p.Arg6Ser	missense	Exon 1 of 11	ENSP00000323047.6	Q9BT17-1
MTG1	ENST00000477902.6	TSL:3	c.-12+52C>A		intron	N/A	ENSP00000475596.1	U3KQ69
ENSG00000254536	ENST00000468317.3	TSL:5	n.*37-1477C>A		intron	N/A	ENSP00000436767.2	B0QZA9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.33e-7

AC:

AN:

1364356

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

673216

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

27938

American (AMR)

AF:

0.00

AC:

AN:

33878

Ashkenazi Jewish (ASJ)

AF:

0.0000413

AC:

AN:

24226

East Asian (EAS)

AF:

0.00

AC:

AN:

32042

South Asian (SAS)

AF:

0.00

AC:

AN:

77306

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4138

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1069042

Other (OTH)

AF:

0.00

AC:

AN:

56804

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.027

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.68

M_CAP

Benign

0.011

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

1.9

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.43

REVEL

Benign

0.055

Sift

Benign

0.039

Sift4G

Benign

0.090

Polyphen

0.042

Vest4

0.36

MutPred

0.37

Loss of MoRF binding (P = 2e-04)

MVP

0.25

MPC

0.026

ClinPred

0.26

GERP RS

0.75

PromoterAI

0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.10

gMVP

0.39

Mutation Taster

=91/9

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over