rs2854138

Variant names:

• chrM-5711-A-G
• rs2854138
• unassigned_transcript_4796:c.19T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP6_Moderate BP7 BS1 BS2

The ENST00000000000(TRNN):​c.19T>C​(p.Leu7Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0062 (AC: 380)
• Consequence: TRNN ENST00000000000 synonymous
• Scores: Mitotip Benign 3.2
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.615
• Publications: 4 publications found

Genes affected

TRNN (HGNC:7493): (mitochondrially encoded tRNA asparagine)

MT-CO1 (HGNC:7419): (mitochondrially encoded cytochrome c oxidase I) Contributes to cytochrome-c oxidase activity. Predicted to be involved in electron transport coupled proton transport and mitochondrial electron transport, cytochrome c to oxygen. Part of mitochondrial respiratory chain complex III and mitochondrial respiratory chain complex IV. [provided by Alliance of Genome Resources, Apr 2022]

MT-ND2 (HGNC:7456): (mitochondrially encoded NADH dehydrogenase 2) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; multiple sclerosis; myocardial infarction; neurodegenerative disease (multiple); and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

TRNA (HGNC:7475): (mitochondrially encoded tRNA alanine)

TRNW (HGNC:7501): (mitochondrially encoded tRNA tryptophan)

TRNC (HGNC:7477): (mitochondrially encoded tRNA cysteine)

TRNY (HGNC:7502): (mitochondrially encoded tRNA tyrosine)

TRNY Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP6: Variant M-5711-A-G is Benign according to our data. Variant chrM-5711-A-G is described in ClinVar as Benign. ClinVar VariationId is 689979.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.615 with no splicing effect.
• BS1: High frequency in mitomap database: 0.0062
• BS2: High AC in GnomadMitoHomoplasmic at 133

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000387400.1. 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-TN	ENST00000387400.1	TSL:6	n.19T>C		non_coding_transcript_exon	Exon 1 of 1
	MT-CO1	ENST00000361624.2	TSL:6	c.-193A>G		upstream_gene	N/A	ENSP00000354499.2
	MT-ND2	ENST00000361453.3	TSL:6	c.*200A>G		downstream_gene	N/A	ENSP00000355046.4

Frequencies

Mitomap GenBank AF: 0.0062 AC: 380

Gnomad homoplasmic AF: 0.0024 AC: 133 AN: 56430

Gnomad heteroplasmic AF: 0.000018 AC: 1 AN: 56430

Mitomap

No disease associated.

ClinVar

ClinVar submissions as Germline

Significance: 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	3.2
Hmtvar	Benign	0.0
PhyloP100		-0.61

Other links and lift over

dbSNP: rs2854138; hg19: chrM-5712;