rs1057516057

Variant names:

• chrM-3275-C-A
• rs1057516057
• unassigned_transcript_4788:c.46C>A

Your query was ambiguous. Multiple possible variants found:

• chrM-3275-C-A
• chrM-3275-C-G
• chrM-3275-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The ENST00000000000(TRNL1):​c.46C>A​(p.Gln16Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 3/3 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0 (AC: 3)
• Consequence: TRNL1 ENST00000000000 missense
• Scores: Mitotip Benign 2.0
• Clinical Significance: Likely benign criteria provided, single submitter B:1 LHON,Metabolic-syndrome-and-polycystic-ovary-syndrome-/-LHON
• Conservation: PhyloP100: -3.37
• Publications: 0 publications found

Genes affected

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

MT-ND1 (HGNC:7455): (mitochondrially encoded NADH dehydrogenase 1) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Located in mitochondrial membrane. Part of mitochondrial respiratory chain complex I. Implicated in several diseases, including MELAS syndrome; neurodegenerative disease (multiple); optic nerve disease (multiple); toxic shock syndrome; and type 2 diabetes mellitus. Biomarker of Alzheimer's disease; Parkinson's disease; and multiple sclerosis. [provided by Alliance of Genome Resources, Apr 2022]

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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very low frequency in mitomap database: 0.0
• BP6: Variant M-3275-C-A is Benign according to our data. Variant chrM-3275-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 689867.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000386347.1. 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-TL1	ENST00000386347.1	TSL:6	n.46C>A		non_coding_transcript_exon	Exon 1 of 1
	MT-ND1	ENST00000361390.2	TSL:6	c.-32C>A		upstream_gene	N/A	ENSP00000354687.2
	MT-RNR2	ENST00000387347.2	TSL:6	n.*46C>A		downstream_gene	N/A

Frequencies

Mitomap GenBank AF: 0.0 AC: 3

Gnomad homoplasmic AF: 0.000035 AC: 2 AN: 56433

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56433

Mitomap

Disease(s): LHON,Metabolic-syndrome-and-polycystic-ovary-syndrome-/-LHON

Status: Reported,Reported

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	MELAS syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Mitotip	Benign	2.0
Hmtvar	Benign	0.10
PhyloP100		-3.4

Other links and lift over

dbSNP: rs1057516057; hg19: chrM-3276;