6-73492090-C-T

Variant names:

• chr6-73492090-C-T
• rs514582
• NM_012123.4:c.1638-144C>T

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MTO1	NM_012123.4	c.1638-144C>T		intron_variant	Intron 9 of 11	ENST00000498286.6	NP_036255.2
MTO1	NM_001123226.2	c.1758-144C>T		intron_variant	Intron 10 of 12		NP_001116698.1
MTO1	NM_133645.3	c.1713-144C>T		intron_variant	Intron 10 of 12		NP_598400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTO1	ENST00000498286.6	c.1638-144C>T		intron_variant	Intron 9 of 11	1	NM_012123.4	ENSP00000419561.2

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 AC: 4645 AN: 10444

Gnomad4 AMR exome AF: 0.623 AC: 10560 AN: 16962

Gnomad4 ASJ exome AF: 0.633 AC: 6992 AN: 11052

Gnomad4 EAS exome AF: 0.508 AC: 12167 AN: 23934

Gnomad4 SAS exome AF: 0.707 AC: 31298 AN: 44274

Gnomad4 FIN exome AF: 0.707 AC: 15050 AN: 21290

Gnomad4 NFE exome AF: 0.701 AC: 163907 AN: 233732

Gnomad4 Remaining exome AF: 0.655 AC: 13772 AN: 21040

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 AC: 0.480903 AN: 0.480903

Gnomad4 AMR AF: 0.617 AC: 0.616671 AN: 0.616671

Gnomad4 ASJ AF: 0.653 AC: 0.652528 AN: 0.652528

Gnomad4 EAS AF: 0.548 AC: 0.548011 AN: 0.548011

Gnomad4 SAS AF: 0.725 AC: 0.724659 AN: 0.724659

Gnomad4 FIN AF: 0.729 AC: 0.728958 AN: 0.728958

Gnomad4 NFE AF: 0.704 AC: 0.704035 AN: 0.704035

Gnomad4 OTH AF: 0.611 AC: 0.611328 AN: 0.611328

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

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.6
DANN	Benign	0.48
Mutation Taster		=100/0	polymorphism (auto)

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;