NM_012123.4:c.1260+191G>T

Variant names:

• chr6-73480996-G-T
• rs1241914180
• NM_012123.4:c.1260+191G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_012123.4(MTO1):​c.1260+191G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.000050 (0 hom., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MTO1 NM_012123.4 intron
• Scores: Splicing: ADA: 0.9999
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800

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 Uncertain_significance. Variant got 4 ACMG points.

• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. Scorers claiming Uncertain: max_spliceai. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTO1	NM_012123.4	c.1260+191G>T		intron_variant	Intron 7 of 11	ENST00000498286.6	NP_036255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTO1	ENST00000498286.6	c.1260+191G>T		intron_variant	Intron 7 of 11	1	NM_012123.4	ENSP00000419561.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 5 AN: 99990 Hom.: 0 Cov.: 22 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000291

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000323

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000760

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 364420 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 193368

Gnomad4 AFR exome AF: 0.00

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0000500 AC: 5 AN: 100018 Hom.: 0 Cov.: 22 AF XY: 0.0000883 AC XY: 4 AN XY: 45288

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000290

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000324

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000760

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	19
DANN	Benign	0.76
Eigen	Benign	0.11
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.013	N
GERP RS		1.4

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.72
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: 5

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

Publications

LitVar

Other links and lift over

dbSNP: rs1241914180; hg19: chr6-74190719;