NM_012123.4:c.1642C>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_012123.4(MTO1):c.1642C>G(p.Leu548Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000243 in 1,606,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L548F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

MTO1
NM_012123.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 2.16

Publications

2 publications found

Variant links:

Genes affected

MTO1 (HGNC:19261): (mitochondrial tRNA translation optimization 1) This gene encodes a mitochondrial protein thought to be involved in mitochondrial tRNA modification. The encoded protein may also play a role in the expression of the non-syndromic and aminoglycoside-induced deafness phenotypes associated with a specific mutation in the mitochondrial 12S rRNA gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MTO1 links:

EEF1A1 (HGNC:3189): (eukaryotic translation elongation factor 1 alpha 1) This gene encodes an isoform of the alpha subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This isoform (alpha 1) is expressed in brain, placenta, lung, liver, kidney, and pancreas, and the other isoform (alpha 2) is expressed in brain, heart and skeletal muscle. This isoform is identified as an autoantigen in 66% of patients with Felty syndrome. This gene has been found to have multiple copies on many chromosomes, some of which, if not all, represent different pseudogenes. [provided by RefSeq, Jul 2008]

EEF1A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1108951).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012123.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTO1	NM_012123.4	MANE Select	c.1642C>G	p.Leu548Val	missense	Exon 10 of 12	NP_036255.2	Q9Y2Z2-4
MTO1	NM_001123226.2		c.1762C>G	p.Leu588Val	missense	Exon 11 of 13	NP_001116698.1	Q9Y2Z2-6
MTO1	NM_133645.3		c.1717C>G	p.Leu573Val	missense	Exon 11 of 13	NP_598400.1	Q9Y2Z2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTO1	ENST00000498286.6	TSL:1 MANE Select	c.1642C>G	p.Leu548Val	missense	Exon 10 of 12	ENSP00000419561.2	Q9Y2Z2-4
MTO1	ENST00000415954.6	TSL:1	c.1762C>G	p.Leu588Val	missense	Exon 11 of 13	ENSP00000402038.2	Q9Y2Z2-6
MTO1	ENST00000370300.8	TSL:1	c.1717C>G	p.Leu573Val	missense	Exon 11 of 13	ENSP00000359323.4	Q9Y2Z2-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000517

AC:

AN:

251270

AF XY:

0.0000810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000254

AC:

AN:

1454350

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

724044

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33320

American (AMR)

AF:

0.0000224

AC:

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26076

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.000232

AC:

AN:

86076

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.000521

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00000724

AC:

AN:

1105268

Other (OTH)

AF:

0.0000831

AC:

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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

AF:

0.0000132

AC:

AN:

151966

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41344

American (AMR)

AF:

0.00

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10544

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

Eigen

Benign

-0.073

Eigen_PC

Benign

0.018

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

M_CAP

Benign

0.0060

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

2.2

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.2

REVEL

Benign

0.18

Sift

Benign

0.035

Sift4G

Benign

0.098

Polyphen

0.57

Vest4

0.44

MutPred

0.31

Loss of stability (P = 0.172)

MVP

0.35

MPC

0.81

ClinPred

0.088

GERP RS

4.3

Varity_R

0.091

gMVP

0.37

Mutation Taster

=94/6

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over