ENST00000389680.2:n.746G>A

Variant names:

• chrM-1393-G-A
• rs111033325
• ENST00000389680.2:n.746G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The ENST00000389680.2(MT-RNR1):​n.746G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0020 (AC: 120)
• Consequence: MT-RNR1 ENST00000389680.2 non_coding_transcript_exon
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -3.52
• Publications: 2 publications found

Genes affected

MT-RNR1 (HGNC:7470): (mitochondrially encoded 12S RNA) Enables DNA binding activity and DNA-binding transcription factor binding activity. Involved in several processes, including osteoblast proliferation; regulation of carbohydrate utilization; and regulation of phosphate metabolic process. Located in extracellular space; mitochondrion; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TRNV (HGNC:7500): (mitochondrially encoded tRNA valine)

TRNV Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• Leigh syndrome

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP6: Variant M-1393-G-A is Benign according to our data. Variant chrM-1393-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 42217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 103

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.746G>A		non_coding_transcript_exon_variant	Exon 1 of 1
TRNV	unassigned_transcript_4786	c.-209G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-RNR1	ENST00000389680.2	n.746G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-TV	ENST00000387342.1	n.-209G>A		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0020 AC: 120

Gnomad homoplasmic AF: 0.0018 AC: 103 AN: 56421

Gnomad heteroplasmic AF: 0.000089 AC: 5 AN: 56421

Alfa AF: 0.00194 Hom.: 18

Mitomap

No disease associated.

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Aug 11, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

m.1393G>A in MT-RNR1: This variant is not expected to have clinical significance because it is a common variant across multiple haplotypes in a human phylogenet ic database (mito map database: mitomap.org). Although this variant has been ide ntified in 1 Saudi individual with Leber's hereditary optic neuropathy (LHON; A bu-Amero 2006) and 1 Chinese individual with aminoglycoside induced hearing loss (Lu 2010), it has been seen in 26/159 (16.3%) Saudi controls (Abu-Amero 2006) a nd has also been identified in the general population at a frequency of 0.16% (4 9/29867) human mitochondrial DNA sequences (mito map database: mitomap.org). -

not provided Benign:1

Dec 29, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism

Other links and lift over

dbSNP: rs111033325; hg19: chrM-1395;