6-73492103-CAAAAAA-CAAAAAAA

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_012123.4(MTO1):​c.1638-116dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000028 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: MTO1 NM_012123.4 intron
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

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

Frequencies

GnomAD3 genomes AF: 0.0000283 AC: 4 AN: 141260 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000712

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000308

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00150 AC: 515 AN: 343598 Hom.: 0 Cov.: 0 AF XY: 0.00134 AC XY: 248 AN XY: 185302

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00194 AC: 17 AN: 8762

American (AMR) AF: 0.00843 AC: 128 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.000873 AC: 8 AN: 9166

East Asian (EAS) AF: 0.00276 AC: 58 AN: 21012

South Asian (SAS) AF: 0.000656 AC: 27 AN: 41178

European-Finnish (FIN) AF: 0.00121 AC: 23 AN: 19064

Middle Eastern (MID) AF: 0.000704 AC: 1 AN: 1420

European-Non Finnish (NFE) AF: 0.00111 AC: 233 AN: 209786

Other (OTH) AF: 0.00111 AC: 20 AN: 18020

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000283 AC: 4 AN: 141260 Hom.: 0 Cov.: 0 AF XY: 0.0000440 AC XY: 3 AN XY: 68114

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000265 AC: 1 AN: 37672

American (AMR) AF: 0.0000712 AC: 1 AN: 14050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3370

East Asian (EAS) AF: 0.00 AC: 0 AN: 4894

South Asian (SAS) AF: 0.00 AC: 0 AN: 4492

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.0000308 AC: 2 AN: 65024

Other (OTH) AF: 0.00 AC: 0 AN: 1932

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0686974), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 706

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.024

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;