6-73492103-CAAAAAA-CAAAA

Variant names:

• chr6-73492103-CAA-C
• rs5877369
• NM_012123.4:c.1638-117_1638-116delAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_012123.4(MTO1):​c.1638-117_1638-116delAA 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
• Publications: 0 publications found

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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012123.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTO1	NM_012123.4	MANE Select	c.1638-117_1638-116delAA		intron	N/A	NP_036255.2	Q9Y2Z2-4
	MTO1	NM_001123226.2		c.1758-117_1758-116delAA		intron	N/A	NP_001116698.1	Q9Y2Z2-6
	MTO1	NM_133645.3		c.1713-117_1713-116delAA		intron	N/A	NP_598400.1	Q9Y2Z2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTO1	ENST00000498286.6	TSL:1 MANE Select	c.1638-117_1638-116delAA		intron	N/A	ENSP00000419561.2	Q9Y2Z2-4
	MTO1	ENST00000415954.6	TSL:1	c.1758-117_1758-116delAA		intron	N/A	ENSP00000402038.2	Q9Y2Z2-6
	MTO1	ENST00000370300.8	TSL:1	c.1713-117_1713-116delAA		intron	N/A	ENSP00000359323.4	Q9Y2Z2-1

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

African (AFR) AF: 0.342 AC: 2787 AN: 8154

American (AMR) AF: 0.309 AC: 4453 AN: 14432

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 3689 AN: 8926

East Asian (EAS) AF: 0.397 AC: 8148 AN: 20520

South Asian (SAS) AF: 0.445 AC: 17700 AN: 39798

European-Finnish (FIN) AF: 0.394 AC: 7302 AN: 18510

Middle Eastern (MID) AF: 0.435 AC: 604 AN: 1388

European-Non Finnish (NFE) AF: 0.405 AC: 82181 AN: 203040

Other (OTH) AF: 0.397 AC: 6927 AN: 17460

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

African (AFR) AF: 0.205 AC: 7749 AN: 37722

American (AMR) AF: 0.273 AC: 3840 AN: 14042

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1284 AN: 3370

East Asian (EAS) AF: 0.441 AC: 2149 AN: 4876

South Asian (SAS) AF: 0.506 AC: 2265 AN: 4480

European-Finnish (FIN) AF: 0.323 AC: 2786 AN: 8626

Middle Eastern (MID) AF: 0.339 AC: 95 AN: 280

European-Non Finnish (NFE) AF: 0.359 AC: 23323 AN: 64992

Other (OTH) AF: 0.348 AC: 679 AN: 1952

Alfa AF: 0.293 Hom.: 706

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.024
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

Other links and lift over

dbSNP: rs5877369; hg19: chr6-74201826;