rs1554150837
Variant names:
Variant summary
Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_012123.4(MTO1):c.1827A>G(p.Gln609Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
MTO1
NM_012123.4 synonymous
NM_012123.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.452
Publications
0 publications found
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]
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]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 6-73497806-A-G is Benign according to our data. Variant chr6-73497806-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 473196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.452 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MTO1 | NM_012123.4 | c.1827A>G | p.Gln609Gln | synonymous_variant | Exon 11 of 12 | ENST00000498286.6 | NP_036255.2 | |
| MTO1 | NM_001123226.2 | c.1947A>G | p.Gln649Gln | synonymous_variant | Exon 12 of 13 | NP_001116698.1 | ||
| MTO1 | NM_133645.3 | c.1902A>G | p.Gln634Gln | synonymous_variant | Exon 12 of 13 | NP_598400.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
30
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461628Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 727122 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
8
AN:
1461628
Hom.:
Cov.:
30
AF XY:
AC XY:
6
AN XY:
727122
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33472
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26132
East Asian (EAS)
AF:
AC:
0
AN:
39682
South Asian (SAS)
AF:
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
AC:
0
AN:
53396
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
8
AN:
1111820
Other (OTH)
AF:
AC:
0
AN:
60380
⚠️ 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: 0.400
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<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
GnomAD4 genome
Cov.:
30
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency Benign:1
May 03, 2017
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not provided Benign:1
Jul 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
MTO1: PM2:Supporting, BP4, BP7 -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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