M-1393-G-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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000389680.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-RNR1	ENST00000389680.2	TSL:6	n.746G>A		non_coding_transcript_exon	Exon 1 of 1
	MT-TV	ENST00000387342.1	TSL:6	n.-209G>A		upstream_gene	N/A

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 v4.9

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

Other links and lift over

dbSNP: rs111033325; hg19: chrM-1395;