6-73492090-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012123.4(MTO1):c.1638-144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 531,814 control chromosomes in the GnomAD database, including 118,648 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (29620 hom., cov: 26)
  • Exomes 𝑓: 0.67 (89028 hom.)
• Consequence: MTO1 NM_012123.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.205

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 6-73492090-C-T is Benign according to our data. Variant chr6-73492090-C-T is described in ClinVar as [Benign]. Clinvar id is 1291360.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTO1	NM_012123.4	c.1638-144C>T		intron_variant		ENST00000498286.6
MTO1	NM_001123226.2	c.1758-144C>T		intron_variant
MTO1	NM_133645.3	c.1713-144C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTO1	ENST00000498286.6	c.1638-144C>T		intron_variant		1	NM_012123.4	P1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 93006 AN: 147388 Hom.: 29624 Cov.: 26

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.569

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.617

GnomAD4 exome AF: 0.675 AC: 259310 AN: 384316 Hom.: 89028 Cov.: 5 AF XY: 0.677 AC XY: 139734 AN XY: 206390

Gnomad4 AFR exome AF: 0.445

Gnomad4 AMR exome AF: 0.623

Gnomad4 ASJ exome AF: 0.633

Gnomad4 EAS exome AF: 0.508

Gnomad4 SAS exome AF: 0.707

Gnomad4 FIN exome AF: 0.707

Gnomad4 NFE exome AF: 0.701

Gnomad4 OTH exome AF: 0.655

GnomAD4 genome AF: 0.631 AC: 93030 AN: 147498 Hom.: 29620 Cov.: 26 AF XY: 0.636 AC XY: 45598 AN XY: 71710

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.725

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.611

Alfa AF: 0.647 Hom.: 3832

Bravo AF: 0.602

Asia WGS AF: 0.547 AC: 1901 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	3.6
Dann	Benign	0.48

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: rs514582; hg19: chr6-74201813; COSMIC: COSV64775444; COSMIC: COSV64775444;