6-73461661-C-G

Variant names:

• chr6-73461661-C-G
• rs12198468
• ENST00000415954.6:c.-194C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000415954.6(MTO1):​c.-194C>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 0.0000219 in 320,274 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: 34)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: MTO1 ENST00000415954.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54
• Publications: 4 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: 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=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTO1	NM_012123.4	c.-194C>G		upstream_gene_variant		ENST00000498286.6	NP_036255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTO1	ENST00000498286.6	c.-194C>G		upstream_gene_variant		1	NM_012123.4	ENSP00000419561.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.0000219 AC: 7 AN: 320274 Hom.: 0 Cov.: 0 AF XY: 0.0000121 AC XY: 2 AN XY: 165546

African (AFR) AF: 0.00 AC: 0 AN: 9498

American (AMR) AF: 0.00 AC: 0 AN: 11000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10414

East Asian (EAS) AF: 0.00 AC: 0 AN: 25426

South Asian (SAS) AF: 0.00 AC: 0 AN: 17230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1468

European-Non Finnish (NFE) AF: 0.0000255 AC: 5 AN: 196194

Other (OTH) AF: 0.000102 AC: 2 AN: 19576

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.17
DANN	Benign	0.26
PhyloP100		-1.5
PromoterAI		0.025	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

Other links and lift over

dbSNP: rs12198468; hg19: chr6-74171384;