6-73461661-C-A

Position:

• chr6-73461661-C-A

Variant summary

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

The ENST00000415954(MTO1):​c.-194C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 472,276 control chromosomes in the GnomAD database, including 198,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.90 (62035 hom., cov: 34)
  • Exomes 𝑓: 0.92 (136491 hom.)
• Consequence: MTO1 ENST00000415954 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.54

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-73461661-C-A is Benign according to our data. Variant chr6-73461661-C-A is described in ClinVar as [Benign]. Clinvar id is 1272952.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	Protein	UniProt
		n.73461661C>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTO1	ENST00000415954	c.-194C>A		5_prime_UTR_variant	1/13	1		ENSP00000402038.2
MTO1	ENST00000681094.1	n.-194C>A		upstream_gene_variant				ENSP00000505394.1

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137120 AN: 152006 Hom.: 61993 Cov.: 34

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: 0.923 AC: 295416 AN: 320152 Hom.: 136491 Cov.: 0 AF XY: 0.922 AC XY: 152650 AN XY: 165492

Gnomad4 AFR exome AF: 0.863

Gnomad4 AMR exome AF: 0.893

Gnomad4 ASJ exome AF: 0.846

Gnomad4 EAS exome AF: 0.925

Gnomad4 SAS exome AF: 0.927

Gnomad4 FIN exome AF: 0.954

Gnomad4 NFE exome AF: 0.928

Gnomad4 OTH exome AF: 0.911

GnomAD4 genome AF: 0.902 AC: 137220 AN: 152124 Hom.: 62035 Cov.: 34 AF XY: 0.903 AC XY: 67178 AN XY: 74388

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.873

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: 0.911 Hom.: 7861

Bravo AF: 0.896

Asia WGS AF: 0.940 AC: 3210 AN: 3414

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	-0.80
CADD	Benign	0.15
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs12198468; hg19: chr6-74171384;