rs117757245

Variant names:

• chr6-73497873-C-G
• rs117757245
• NM_012123.4:c.1894C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-73497873-C-G
• chr6-73497873-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001123226.2(MTO1):​c.2014C>G​(p.Leu672Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L672L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MTO1 NM_001123226.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549
• Publications: 5 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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123226.2. 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.1894C>G	p.Leu632Val	missense	Exon 11 of 12	NP_036255.2
	MTO1	NM_001123226.2		c.2014C>G	p.Leu672Val	missense	Exon 12 of 13	NP_001116698.1
	MTO1	NM_133645.3		c.1969C>G	p.Leu657Val	missense	Exon 12 of 13	NP_598400.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTO1	ENST00000498286.6	TSL:1 MANE Select	c.1894C>G	p.Leu632Val	missense	Exon 11 of 12	ENSP00000419561.2
	MTO1	ENST00000415954.6	TSL:1	c.2014C>G	p.Leu672Val	missense	Exon 12 of 13	ENSP00000402038.2
	MTO1	ENST00000370300.8	TSL:1	c.1969C>G	p.Leu657Val	missense	Exon 12 of 13	ENSP00000359323.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D
Eigen	Benign	0.18
Eigen_PC	Benign	0.055
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Pathogenic	4.7	H
PhyloP100		0.55
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.73		Gain of methylation at K656 (P = 0.0494)
MVP		0.53
MPC		0.29
ClinPred		1.0	D
GERP RS		2.9
Varity_R		0.21
gMVP		0.75
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs117757245; hg19: chr6-74207596;