6-73491003-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012123.4(MTO1):​c.1638-1231A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,958 control chromosomes in the GnomAD database, including 26,828 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.58 ( 26828 hom., cov: 32)

Consequence

MTO1
NM_012123.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.951

Publications

10 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]
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTO1NM_012123.4 linkc.1638-1231A>G intron_variant Intron 9 of 11 ENST00000498286.6 NP_036255.2 Q9Y2Z2-4
MTO1NM_001123226.2 linkc.1758-1231A>G intron_variant Intron 10 of 12 NP_001116698.1 Q9Y2Z2-6
MTO1NM_133645.3 linkc.1713-1231A>G intron_variant Intron 10 of 12 NP_598400.1 Q9Y2Z2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTO1ENST00000498286.6 linkc.1638-1231A>G intron_variant Intron 9 of 11 1 NM_012123.4 ENSP00000419561.2 Q9Y2Z2-4

Frequencies

GnomAD3 genomes
AF:
0.581
AC:
88181
AN:
151838
Hom.:
26841
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.422
Gnomad AMI
AF:
0.740
Gnomad AMR
AF:
0.449
Gnomad ASJ
AF:
0.639
Gnomad EAS
AF:
0.458
Gnomad SAS
AF:
0.680
Gnomad FIN
AF:
0.684
Gnomad MID
AF:
0.554
Gnomad NFE
AF:
0.688
Gnomad OTH
AF:
0.576
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.580
AC:
88162
AN:
151958
Hom.:
26828
Cov.:
32
AF XY:
0.581
AC XY:
43145
AN XY:
74264
show subpopulations
African (AFR)
AF:
0.421
AC:
17462
AN:
41450
American (AMR)
AF:
0.448
AC:
6834
AN:
15244
Ashkenazi Jewish (ASJ)
AF:
0.639
AC:
2216
AN:
3470
East Asian (EAS)
AF:
0.458
AC:
2360
AN:
5152
South Asian (SAS)
AF:
0.679
AC:
3276
AN:
4822
European-Finnish (FIN)
AF:
0.684
AC:
7227
AN:
10564
Middle Eastern (MID)
AF:
0.538
AC:
157
AN:
292
European-Non Finnish (NFE)
AF:
0.688
AC:
46752
AN:
67944
Other (OTH)
AF:
0.571
AC:
1206
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1781
3562
5342
7123
8904
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
754
1508
2262
3016
3770
<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:
0.634
Hom.:
93649
Bravo
AF:
0.554
Asia WGS
AF:
0.488
AC:
1700
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
0.14
DANN
Benign
0.71
PhyloP100
-0.95
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs577372; hg19: chr6-74200726; API