6-73461744-C-G

Position:

• chr6-73461744-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012123.4(MTO1):​c.-111C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 1,092,352 control chromosomes in the GnomAD database, including 470,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.90 (62071 hom., cov: 35)
  • Exomes 𝑓: 0.93 (408054 hom.)
• Consequence: MTO1 NM_012123.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.644

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 6-73461744-C-G is Benign according to our data. Variant chr6-73461744-C-G is described in ClinVar as [Benign]. Clinvar id is 1291359.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-73461744-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTO1	NM_012123.4	c.-111C>G		5_prime_UTR_variant	1/12	ENST00000498286.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTO1	ENST00000498286.6	c.-111C>G		5_prime_UTR_variant	1/12	1	NM_012123.4	P1

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137203 AN: 152110 Hom.: 62029 Cov.: 35

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.927

Gnomad OTH AF: 0.886

GnomAD4 exome AF: 0.931 AC: 875049 AN: 940124 Hom.: 408054 Cov.: 13 AF XY: 0.930 AC XY: 438028 AN XY: 470836

Gnomad4 AFR exome AF: 0.863

Gnomad4 AMR exome AF: 0.890

Gnomad4 ASJ exome AF: 0.850

Gnomad4 EAS exome AF: 0.932

Gnomad4 SAS exome AF: 0.930

Gnomad4 FIN exome AF: 0.953

Gnomad4 NFE exome AF: 0.937

Gnomad4 OTH exome AF: 0.919

GnomAD4 genome AF: 0.902 AC: 137303 AN: 152228 Hom.: 62071 Cov.: 35 AF XY: 0.903 AC XY: 67216 AN XY: 74436

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.842

Gnomad4 EAS AF: 0.954

Gnomad4 SAS AF: 0.931

Gnomad4 FIN AF: 0.956

Gnomad4 NFE AF: 0.927

Gnomad4 OTH AF: 0.886

Alfa AF: 0.903 Hom.: 2983

Bravo AF: 0.896

Asia WGS AF: 0.939 AC: 3179 AN: 3388

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.8
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1713862; hg19: chr6-74171467;