ENST00000361624.2:c.-248A>G

Variant names:

• chrM-5656-A-G
• rs41453547
• ENST00000361624.2:c.-248A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000361624.2(MT-CO1):​c.-248A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Mitomap GenBank: 𝑓 0.012 (AC: 748)
• Consequence: MT-CO1 ENST00000361624.2 upstream_gene
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -2.98
• Publications: 2 publications found

Genes affected

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)

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

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 -8 ACMG points.

• BA1: High frequency in mitomap database: 0.012200001

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX1	unassigned_transcript_4799	c.-248A>G		upstream_gene_variant
TRNA	unassigned_transcript_4795	c.-1T>C		upstream_gene_variant
ND2	unassigned_transcript_4793	c.*145A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-CO1	ENST00000361624.2	c.-248A>G		upstream_gene_variant		6		ENSP00000354499.2
MT-ND2	ENST00000361453.3	c.*145A>G		downstream_gene_variant		6		ENSP00000355046.4

Frequencies

Mitomap GenBank AF: 0.012 AC: 748

Gnomad homoplasmic AF: 0.021 AC: 1171 AN: 56424

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56424

Alfa AF: 0.0130 Hom.: 48

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-3.0

Other links and lift over

dbSNP: rs41453547; hg19: chrM-5657;