6-73491915-G-A

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.1638-319G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 217,114 control chromosomes in the GnomAD database, including 3,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2862 hom., cov: 31)
  • Exomes 𝑓: 0.17 (974 hom.)
• Consequence: MTO1 NM_012123.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.62

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=-1.02).
• BP6: Variant 6-73491915-G-A is Benign according to our data. Variant chr6-73491915-G-A is described in ClinVar as [Benign]. Clinvar id is 1257484.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTO1	NM_012123.4	c.1638-319G>A		intron_variant		ENST00000498286.6
MTO1	NM_001123226.2	c.1758-319G>A		intron_variant
MTO1	NM_133645.3	c.1713-319G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTO1	ENST00000498286.6	c.1638-319G>A		intron_variant		1	NM_012123.4	P1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29080 AN: 151704 Hom.: 2854 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.171 AC: 11197 AN: 65290 Hom.: 974 AF XY: 0.171 AC XY: 5942 AN XY: 34796

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.166

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.192 AC: 29115 AN: 151824 Hom.: 2862 Cov.: 31 AF XY: 0.190 AC XY: 14103 AN XY: 74204

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.192

Alfa AF: 0.189 Hom.: 325

Bravo AF: 0.192

Asia WGS AF: 0.228 AC: 792 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 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.4
Dann	Benign	0.78

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: rs10943096; hg19: chr6-74201638;