6-73482532-G-T

Position:

• chr6-73482532-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012123.4(MTO1):​c.1549G>T​(p.Val517Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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: 6.8e-7 (0 hom.)
• Consequence: MTO1 NM_012123.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.51

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06711921).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTO1	NM_012123.4	c.1549G>T	p.Val517Leu	missense_variant	9/12	ENST00000498286.6	NP_036255.2
MTO1	NM_001123226.2	c.1669G>T	p.Val557Leu	missense_variant	10/13		NP_001116698.1
MTO1	NM_133645.3	c.1624G>T	p.Val542Leu	missense_variant	10/13		NP_598400.1
MTO1	XM_047418605.1	c.*27G>T		3_prime_UTR_variant	8/8		XP_047274561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTO1	ENST00000498286.6	c.1549G>T	p.Val517Leu	missense_variant	9/12	1	NM_012123.4	ENSP00000419561	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460422 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726588

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.37
DEOGEN2	Benign	0.078	.;.;.;T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D;D;D;D;D
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.067	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	.;.;.;N;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.26	N;N;N;N;N
REVEL	Benign	0.087
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0	B;B;.;B;.
Vest4		0.40
MutPred		0.45		.;.;.;Loss of MoRF binding (P = 0.1029);.;
MVP		0.32
MPC		0.27
ClinPred		0.29	T
GERP RS		4.5
Varity_R		0.041
gMVP		0.46

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

LitVar

Other links and lift over

dbSNP: rs139608228; hg19: chr6-74192255;