NM_012123.4:c.60_61delTCinsAA

Variant names:

• chr6-73461914-TC-AA
• NM_012123.4:c.60_61delTCinsAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_012123.4(MTO1):​c.60_61delTCinsAA​(p.PhePro20LeuThr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTO1 NM_012123.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0260
• 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]

CGAS (HGNC:21367): (cyclic GMP-AMP synthase) Enables several functions, including 2',3'-cyclic GMP-AMP synthase activity; chromatin binding activity; and phosphatidylinositol-4,5-bisphosphate binding activity. Involved in several processes, including cellular response to exogenous dsRNA; positive regulation of intracellular signal transduction; and regulation of defense response. Located in several cellular components, including cytosol; nucleus; and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012123.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTO1	NM_012123.4	MANE Select	c.60_61delTCinsAA	p.PhePro20LeuThr	missense	N/A	NP_036255.2	Q9Y2Z2-4
	MTO1	NM_001123226.2		c.60_61delTCinsAA	p.PhePro20LeuThr	missense	N/A	NP_001116698.1	Q9Y2Z2-6
	MTO1	NM_133645.3		c.60_61delTCinsAA	p.PhePro20LeuThr	missense	N/A	NP_598400.1	Q9Y2Z2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTO1	ENST00000498286.6	TSL:1 MANE Select	c.60_61delTCinsAA	p.PhePro20LeuThr	missense	N/A	ENSP00000419561.2	Q9Y2Z2-4
	MTO1	ENST00000415954.6	TSL:1	c.60_61delTCinsAA	p.PhePro20LeuThr	missense	N/A	ENSP00000402038.2	Q9Y2Z2-6
	MTO1	ENST00000370300.8	TSL:1	c.60_61delTCinsAA	p.PhePro20LeuThr	missense	N/A	ENSP00000359323.4	Q9Y2Z2-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.026

Splicing

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

Other links and lift over

hg19: chr6-74171637;