6-73492103-CAA-C

Position:

• chr6-73492103-CAA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_012123.4(MTO1):​c.1638-117_1638-116del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 473,442 control chromosomes in the GnomAD database, including 10,108 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7146 hom., cov: 0)
  • Exomes 𝑓: 0.40 (2962 hom.)
• Consequence: MTO1 NM_012123.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0240

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 -10 ACMG points.

• BP6: Variant 6-73492103-CAA-C is Benign according to our data. Variant chr6-73492103-CAA-C is described in ClinVar as [Benign]. Clinvar id is 1270647.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTO1	NM_012123.4	c.1638-117_1638-116del		intron_variant		ENST00000498286.6	NP_036255.2
MTO1	NM_001123226.2	c.1758-117_1758-116del		intron_variant			NP_001116698.1
MTO1	NM_133645.3	c.1713-117_1713-116del		intron_variant			NP_598400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTO1	ENST00000498286.6	c.1638-117_1638-116del		intron_variant		1	NM_012123.4	ENSP00000419561	P1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 44585 AN: 141154 Hom.: 7157 Cov.: 0

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.403 AC: 133791 AN: 332228 Hom.: 2962 AF XY: 0.406 AC XY: 72842 AN XY: 179238

Gnomad4 AFR exome AF: 0.342

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.413

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.445

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.397

GnomAD4 genome AF: 0.316 AC: 44558 AN: 141214 Hom.: 7146 Cov.: 0 AF XY: 0.319 AC XY: 21770 AN XY: 68148

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.348

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

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs5877369; hg19: chr6-74201826;