6-73492103-CA-C

Position:

• chr6-73492103-CA-C

Variant summary

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

The ENST00000498286.6(MTO1):​c.1638-116del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (28765 hom., cov: 0)
  • Exomes 𝑓: 0.43 (2586 hom.)
• Consequence: MTO1 ENST00000498286.6 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-CA-C is Benign according to our data. Variant chr6-73492103-CA-C is described in ClinVar as [Benign]. Clinvar id is 1269549.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.638 AC: 89898 AN: 140930 Hom.: 28737 Cov.: 0

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.632

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.617

GnomAD4 exome AF: 0.427 AC: 143562 AN: 336310 Hom.: 2586 Cov.: 0 AF XY: 0.425 AC XY: 76914 AN XY: 181186

Gnomad4 AFR exome AF: 0.478

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.430

Gnomad4 EAS exome AF: 0.394

Gnomad4 SAS exome AF: 0.381

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.437

Gnomad4 OTH exome AF: 0.431

GnomAD4 genome AF: 0.638 AC: 89969 AN: 140990 Hom.: 28765 Cov.: 0 AF XY: 0.631 AC XY: 42942 AN XY: 68006

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.574

Gnomad4 ASJ AF: 0.596

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.619

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

Jan 06, 2020

- -

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;