6-73461744-C-G

Variant names:

• chr6-73461744-C-G
• rs1713862
• NM_012123.4:c.-111C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012123.4(MTO1):​c.-111C>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 0.927 in 1,092,352 control chromosomes in the GnomAD database, including 470,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.90 (62071 hom., cov: 35)
  • Exomes 𝑓: 0.93 (408054 hom.)
• Consequence: MTO1 NM_012123.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.644
• Publications: 9 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]

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 6-73461744-C-G is Benign according to our data. Variant chr6-73461744-C-G is described in ClinVar as [Benign]. Clinvar id is 1291359.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTO1	NM_012123.4	c.-111C>G		5_prime_UTR_variant	Exon 1 of 12	ENST00000498286.6	NP_036255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTO1	ENST00000498286.6	c.-111C>G		5_prime_UTR_variant	Exon 1 of 12	1	NM_012123.4	ENSP00000419561.2

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137203 AN: 152110 Hom.: 62029 Cov.: 35

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.886

GnomAD4 exome AF: 0.931 AC: 875049 AN: 940124 Hom.: 408054 Cov.: 13 AF XY: 0.930 AC XY: 438028 AN XY: 470836

African (AFR) AF: 0.863 AC: 19326 AN: 22388

American (AMR) AF: 0.890 AC: 26179 AN: 29400

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 15563 AN: 18318

East Asian (EAS) AF: 0.932 AC: 31600 AN: 33902

South Asian (SAS) AF: 0.930 AC: 56956 AN: 61252

European-Finnish (FIN) AF: 0.953 AC: 44222 AN: 46408

Middle Eastern (MID) AF: 0.864 AC: 3073 AN: 3558

European-Non Finnish (NFE) AF: 0.937 AC: 639248 AN: 682570

Other (OTH) AF: 0.919 AC: 38882 AN: 42328

GnomAD4 genome AF: 0.902 AC: 137303 AN: 152228 Hom.: 62071 Cov.: 35 AF XY: 0.903 AC XY: 67216 AN XY: 74436

African (AFR) AF: 0.854 AC: 35481 AN: 41526

American (AMR) AF: 0.872 AC: 13346 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2916 AN: 3464

East Asian (EAS) AF: 0.954 AC: 4944 AN: 5182

South Asian (SAS) AF: 0.931 AC: 4496 AN: 4830

European-Finnish (FIN) AF: 0.956 AC: 10143 AN: 10612

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.927 AC: 63013 AN: 67994

Other (OTH) AF: 0.886 AC: 1872 AN: 2112

Alfa AF: 0.903 Hom.: 2983

Bravo AF: 0.896

Asia WGS AF: 0.939 AC: 3179 AN: 3388

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.8
DANN	Benign	0.67
PhyloP100		0.64
PromoterAI		-0.033	Neutral
Mutation Taster		=298/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1713862; hg19: chr6-74171467;