M-3010-G-A

Variant names:

• chrM-3010-G-A
• rs3928306
• ENST00000387347.2:n.1340G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000000000(RNR2):​n.1340G>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 0.15 (AC: 9387)
• Consequence: RNR2 ENST00000000000 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1 Cyclic-Vomiting-Syndrome-with-Migraine-/-high-altitude-adaptation
• Conservation: PhyloP100: 2.89
• Publications: 32 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: Benign. The variant received -10 ACMG points.

• BP6: Variant M-3010-G-A is Benign according to our data. Variant chrM-3010-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 441149.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: High frequency in mitomap database: 0.1535

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNR2	unassigned_transcript_4787	n.1340G>A		non_coding_transcript_exon_variant	Exon 1 of 1
TRNL1	unassigned_transcript_4788	c.-220G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-RNR2	ENST00000387347.2	n.1340G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
MT-TL1	ENST00000386347.1	n.-220G>A		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.15 AC: 9387

Gnomad homoplasmic AF: 0.16 AC: 9208 AN: 56350

Gnomad heteroplasmic AF: 0.000071 AC: 4 AN: 56350

Alfa AF: 0.134 Hom.: 1654

Mitomap

Disease(s): Cyclic-Vomiting-Syndrome-with-Migraine-/-high-altitude-adaptation

Status: Reported

ClinVar

Significance: Likely benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Other:1

-

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9
Mutation Taster		=100/0	polymorphism

Other links and lift over

dbSNP: rs3928306; hg19: chrM-3012; COSMIC: COSV104421145;