GeneBe

6-73461810-C-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012123.4(MTO1):​c.-45C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,266 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

MTO1
NM_012123.4 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.285

Publications

0 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 Gene-Disease associations (from GenCC):
  • mitochondrial disease
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency
    Inheritance: AR, Unknown Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P

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ACMG classification

Classification was made for transcript

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

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTO1NM_012123.4 linkc.-45C>G 5_prime_UTR_variant Exon 1 of 12 ENST00000498286.6 NP_036255.2 Q9Y2Z2-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTO1ENST00000498286.6 linkc.-45C>G 5_prime_UTR_variant Exon 1 of 12 1 NM_012123.4 ENSP00000419561.2 Q9Y2Z2-4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.99e-7
AC:
1
AN:
1430266
Hom.:
0
Cov.:
29
AF XY:
0.00000141
AC XY:
1
AN XY:
707574
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32712
American (AMR)
AF:
0.00
AC:
0
AN:
43334
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25164
East Asian (EAS)
AF:
0.0000256
AC:
1
AN:
39134
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84478
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52912
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5646
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1087938
Other (OTH)
AF:
0.00
AC:
0
AN:
58948
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
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
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
5.4
DANN
Benign
0.38
PhyloP100
-0.28
PromoterAI
-0.068
Neutral

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: rs375406465; hg19: chr6-74171533; API