6-73491953-A-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.1638-281A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 244,330 control chromosomes in the GnomAD database, including 101,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.90 (62214 hom., cov: 29)
  • Exomes 𝑓: 0.92 (39330 hom.)
• Consequence: MTO1 NM_012123.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.68

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=-1.03).
• BP6: Variant 6-73491953-A-T is Benign according to our data. Variant chr6-73491953-A-T is described in ClinVar as [Benign]. Clinvar id is 682640.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTO1	NM_012123.4	c.1638-281A>T		intron_variant		ENST00000498286.6
MTO1	NM_001123226.2	c.1758-281A>T		intron_variant
MTO1	NM_133645.3	c.1713-281A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTO1	ENST00000498286.6	c.1638-281A>T		intron_variant		1	NM_012123.4	P1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137255 AN: 151840 Hom.: 62173 Cov.: 29

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.887

GnomAD4 exome AF: 0.922 AC: 85192 AN: 92372 Hom.: 39330 AF XY: 0.922 AC XY: 45735 AN XY: 49588

Gnomad4 AFR exome AF: 0.878

Gnomad4 AMR exome AF: 0.894

Gnomad4 ASJ exome AF: 0.834

Gnomad4 EAS exome AF: 0.944

Gnomad4 SAS exome AF: 0.926

Gnomad4 FIN exome AF: 0.947

Gnomad4 NFE exome AF: 0.928

Gnomad4 OTH exome AF: 0.919

GnomAD4 genome AF: 0.904 AC: 137354 AN: 151958 Hom.: 62214 Cov.: 29 AF XY: 0.905 AC XY: 67212 AN XY: 74264

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.873

Gnomad4 ASJ AF: 0.841

Gnomad4 EAS AF: 0.955

Gnomad4 SAS AF: 0.931

Gnomad4 FIN AF: 0.956

Gnomad4 NFE AF: 0.927

Gnomad4 OTH AF: 0.888

Alfa AF: 0.912 Hom.: 7877

Bravo AF: 0.898

Asia WGS AF: 0.939 AC: 3266 AN: 3478

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 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.4
Dann	Benign	0.83

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: rs516203; hg19: chr6-74201676;