ENST00000387347.2:n.1321T>C

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 ENST00000387347.2(MT-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: MT-RNR2 ENST00000387347.2 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: G2P, ClinGen
• 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 id is 9626.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR2	unassigned_transcript_4787	n.1321T>C		non_coding_transcript_exon_variant	Exon 1 of 1
TRNL1	unassigned_transcript_4788	c.-239T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-RNR2	ENST00000387347.2	n.1321T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-TL1	ENST00000386347.1	n.-239T>C		upstream_gene_variant		6

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Chloramphenicol resistance Pathogenic:1

Nov 11, 1981

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7

Other links and lift over

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