NM_012123.4:c.1638-319G>A

Variant names:

• chr6-73491915-G-A
• rs10943096
• NM_012123.4:c.1638-319G>A

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.1638-319G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 217,114 control chromosomes in the GnomAD database, including 3,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2862 hom., cov: 31)
  • Exomes 𝑓: 0.17 (974 hom.)
• Consequence: MTO1 NM_012123.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.62
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 6-73491915-G-A is Benign according to our data. Variant chr6-73491915-G-A is described in ClinVar as Benign. ClinVar VariationId is 1257484.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 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.1638-319G>A		intron	N/A	NP_036255.2	Q9Y2Z2-4
	MTO1	NM_001123226.2		c.1758-319G>A		intron	N/A	NP_001116698.1	Q9Y2Z2-6
	MTO1	NM_133645.3		c.1713-319G>A		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.1638-319G>A		intron	N/A	ENSP00000419561.2	Q9Y2Z2-4
	MTO1	ENST00000415954.6	TSL:1	c.1758-319G>A		intron	N/A	ENSP00000402038.2	Q9Y2Z2-6
	MTO1	ENST00000370300.8	TSL:1	c.1713-319G>A		intron	N/A	ENSP00000359323.4	Q9Y2Z2-1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29080 AN: 151704 Hom.: 2854 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.186

GnomAD4 exome AF: 0.171 AC: 11197 AN: 65290 Hom.: 974 AF XY: 0.171 AC XY: 5942 AN XY: 34796

African (AFR) AF: 0.216 AC: 463 AN: 2142

American (AMR) AF: 0.166 AC: 701 AN: 4234

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 231 AN: 1494

East Asian (EAS) AF: 0.229 AC: 942 AN: 4112

South Asian (SAS) AF: 0.149 AC: 1465 AN: 9824

European-Finnish (FIN) AF: 0.200 AC: 494 AN: 2466

Middle Eastern (MID) AF: 0.161 AC: 30 AN: 186

European-Non Finnish (NFE) AF: 0.168 AC: 6307 AN: 37632

Other (OTH) AF: 0.176 AC: 564 AN: 3200

GnomAD4 genome AF: 0.192 AC: 29115 AN: 151824 Hom.: 2862 Cov.: 31 AF XY: 0.190 AC XY: 14103 AN XY: 74204

African (AFR) AF: 0.219 AC: 9051 AN: 41384

American (AMR) AF: 0.175 AC: 2660 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3464

East Asian (EAS) AF: 0.224 AC: 1148 AN: 5136

South Asian (SAS) AF: 0.165 AC: 795 AN: 4804

European-Finnish (FIN) AF: 0.200 AC: 2106 AN: 10552

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.180 AC: 12207 AN: 67932

Other (OTH) AF: 0.192 AC: 405 AN: 2112

Alfa AF: 0.190 Hom.: 342

Bravo AF: 0.192

Asia WGS AF: 0.228 AC: 792 AN: 3478

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.78
PhyloP100		-1.6
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: rs10943096; hg19: chr6-74201638;