rs199474823

Variant names:

• chrM-2991-T-C
• rs199474823
• ENST00000387347.2:n.1321T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The ENST00000000000(RNR2):​n.1321T>C variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 0)
• Consequence: RNR2 ENST00000000000 non_coding_transcript_exon
• Clinical Significance: Pathogenic no assertion criteria provided P:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 7.68
• Publications: 3 publications found

Genes affected

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]

TRNL1 (HGNC:7490): (mitochondrially encoded tRNA leucine 1 (UUA/G)) Implicated in cardiomyopathy. [provided by Alliance of Genome Resources, Apr 2022]

TRNL1 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE, LIMITED Submitted by: ClinGen, G2P
• maternally-inherited diabetes and deafness

  Inheritance: Mitochondrial Classification: STRONG Submitted by: Genomics England PanelApp
• MERRF syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• PP5: Variant M-2991-T-C is Pathogenic according to our data. Variant chrM-2991-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 9626.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387347.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-RNR2	ENST00000387347.2	TSL:6	n.1321T>C		non_coding_transcript_exon	Exon 1 of 1
	MT-TL1	ENST00000386347.1	TSL:6	n.-239T>C		upstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0 AC: 0

Gnomad homoplasmic AF: 0.0 AC: 0 AN: 56430

Gnomad heteroplasmic AF: 0.000035 AC: 2 AN: 56430

Alfa AF: 0.00 Hom.: 0

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Chloramphenicol resistance (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7

Other links and lift over

dbSNP: rs199474823; hg19: chrM-2993; COSMIC: COSV62294264;