chrM-1462-G-A

Variant names:

• chrM-1462-G-A
• rs111033326
• ENST00000389680.2:n.815G>A

Variant summary

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

The ENST00000000000(RNR1):​n.815G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.0040 (AC: 245)
• Consequence: RNR1 ENST00000000000 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: -3.44
• Publications: 5 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)

MT-RNR2 (HGNC:7471): (mitochondrially encoded 16S RNA) Enables G protein-coupled receptor binding activity; protein self-association; and receptor antagonist activity. Involved in several processes, including leukocyte chemotaxis; negative regulation of cell death; and negative regulation of neuroinflammatory response. Located in several cellular components, including mitochondrion; perinuclear region of cytoplasm; and sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]

MT-RNR2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP6: Variant M-1462-G-A is Benign according to our data. Variant chrM-1462-G-A is described in ClinVar as [Benign]. Clinvar id is 42222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 159

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR1	unassigned_transcript_4785	n.815G>A		non_coding_transcript_exon_variant	Exon 1 of 1
TRNV	unassigned_transcript_4786	c.-140G>A		upstream_gene_variant
RNR2	unassigned_transcript_4787	n.-209G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-RNR1	ENST00000389680.2	n.815G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-TV	ENST00000387342.1	n.-140G>A		upstream_gene_variant		6
MT-RNR2	ENST00000387347.2	n.-209G>A		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0040 AC: 245

Gnomad homoplasmic AF: 0.0028 AC: 159 AN: 56432

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56432

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jun 19, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Nov 16, 2016

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.4

Other links and lift over

dbSNP: rs111033326; hg19: chrM-1464;