6-73492103-CAAAAAA-CAAAAA

Variant names:

• chr6-73492103-CA-C
• rs5877369
• NM_012123.4:c.1638-116delA

Variant summary

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

The NM_012123.4(MTO1):​c.1638-116delA 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 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-CA-C is Benign according to our data. Variant chr6-73492103-CA-C is described in ClinVar as Benign. ClinVar VariationId 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.

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.1638-116delA		intron	N/A	NP_036255.2	Q9Y2Z2-4
	MTO1	NM_001123226.2		c.1758-116delA		intron	N/A	NP_001116698.1	Q9Y2Z2-6
	MTO1	NM_133645.3		c.1713-116delA		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.1638-116delA		intron	N/A	ENSP00000419561.2	Q9Y2Z2-4
	MTO1	ENST00000415954.6	TSL:1	c.1758-116delA		intron	N/A	ENSP00000402038.2	Q9Y2Z2-6
	MTO1	ENST00000370300.8	TSL:1	c.1713-116delA		intron	N/A	ENSP00000359323.4	Q9Y2Z2-1

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

African (AFR) AF: 0.478 AC: 4156 AN: 8688

American (AMR) AF: 0.403 AC: 6028 AN: 14958

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 3870 AN: 9004

East Asian (EAS) AF: 0.394 AC: 8100 AN: 20556

South Asian (SAS) AF: 0.381 AC: 15120 AN: 39670

European-Finnish (FIN) AF: 0.438 AC: 8178 AN: 18680

Middle Eastern (MID) AF: 0.418 AC: 582 AN: 1392

European-Non Finnish (NFE) AF: 0.437 AC: 89913 AN: 205682

Other (OTH) AF: 0.431 AC: 7615 AN: 17680

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

African (AFR) AF: 0.754 AC: 28399 AN: 37684

American (AMR) AF: 0.574 AC: 8060 AN: 14034

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2006 AN: 3366

East Asian (EAS) AF: 0.487 AC: 2371 AN: 4868

South Asian (SAS) AF: 0.453 AC: 2027 AN: 4470

European-Finnish (FIN) AF: 0.627 AC: 5400 AN: 8618

Middle Eastern (MID) AF: 0.639 AC: 179 AN: 280

European-Non Finnish (NFE) AF: 0.614 AC: 39839 AN: 64854

Other (OTH) AF: 0.619 AC: 1202 AN: 1942

Alfa AF: 0.561 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;