rs577372

chr6-73491003-A-Gchr6-73491003-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012123.4(MTO1):c.1638-1231A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,958 control chromosomes in the GnomAD database, including 26,828 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (26828 hom., cov: 32)
• Consequence: MTO1 NM_012123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.951

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTO1	NM_012123.4	c.1638-1231A>G		intron_variant		ENST00000498286.6
MTO1	NM_001123226.2	c.1758-1231A>G		intron_variant
MTO1	NM_133645.3	c.1713-1231A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTO1	ENST00000498286.6	c.1638-1231A>G		intron_variant		1	NM_012123.4	P1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88181 AN: 151838 Hom.: 26841 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.576

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.580 AC: 88162 AN: 151958 Hom.: 26828 Cov.: 32 AF XY: 0.581 AC XY: 43145 AN XY: 74264

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.684

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.571

Alfa AF: 0.652 Hom.: 55974

Bravo AF: 0.554

Asia WGS AF: 0.488 AC: 1700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.14
Dann	Benign	0.71

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: rs577372; hg19: chr6-74200726;