rs386829033

Variant names:

• chrM-8392-G-A
• rs121434446
• ENST00000361851.1:c.27G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7 BS1 BS2

The ENST00000361851.1(MT-ATP8):​c.27G>A​(p.Trp9Trp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Mitomap GenBank: 𝑓 0.0071 (AC: 431)
• Consequence: MT-ATP8 ENST00000361851.1 synonymous
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: 2.89
• Publications: 10 publications found

Genes affected

MT-ATP8 (HGNC:7415): (mitochondrially encoded ATP synthase 8) Contributes to proton-transporting ATP synthase activity, rotational mechanism. Involved in mitochondrial ATP synthesis coupled proton transport. Part of mitochondrial proton-transporting ATP synthase complex. Implicated in multiple sclerosis and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

MT-ATP6 (HGNC:7414): (mitochondrially encoded ATP synthase 6) Contributes to proton-transporting ATP synthase activity, rotational mechanism. Involved in mitochondrial ATP synthesis coupled proton transport. Part of mitochondrial proton-transporting ATP synthase complex. Implicated in Leber hereditary optic neuropathy; NARP syndrome; Parkinson's disease; multiple sclerosis; and systemic lupus erythematosus. [provided by Alliance of Genome Resources, Apr 2022]

MT-CO2 (HGNC:7421): (mitochondrially encoded cytochrome c oxidase II) Contributes to cytochrome-c oxidase activity. Predicted to be involved in mitochondrial electron transport, cytochrome c to oxygen and positive regulation of vasoconstriction. Located in mitochondrial inner membrane. Part of respiratory chain complex IV. Biomarker of Huntington's disease and stomach cancer. [provided by Alliance of Genome Resources, Apr 2022]

TRNK (HGNC:7489): (mitochondrially encoded tRNA lysine)

TRNK Gene-Disease associations (from GenCC):

• Leigh syndrome

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• maternally-inherited cardiomyopathy and hearing loss

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• MERRF syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP7: Synonymous conserved (PhyloP=2.89 with no splicing effect.
• BS1: High frequency in mitomap database: 0.0070999996
• BS2: High AC in GnomadMitoHomoplasmic at 63

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8	unassigned_transcript_4804	c.27G>A	p.Trp9Trp	synonymous_variant	Exon 1 of 1
ATP6	unassigned_transcript_4805	c.-135G>A		upstream_gene_variant
COX2	unassigned_transcript_4802	c.*123G>A		downstream_gene_variant
TRNK	unassigned_transcript_4803	c.*28G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ATP8	ENST00000361851.1	c.27G>A	p.Trp9Trp	synonymous_variant	Exon 1 of 1	6		ENSP00000355265.1
MT-ATP6	ENST00000361899.2	c.-135G>A		upstream_gene_variant		6		ENSP00000354632.2
MT-CO2	ENST00000361739.1	c.*123G>A		downstream_gene_variant		6		ENSP00000354876.1
MT-TK	ENST00000387421.1	n.*28G>A		downstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.0071 AC: 431

Gnomad homoplasmic AF: 0.0011 AC: 63 AN: 56406

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56406

Alfa AF: 0.000445 Hom.: 2

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.42	T
PhyloP100		2.9
GERP RS		2.2
Mutation Taster		=87/13	polymorphism

Other links and lift over

dbSNP: rs121434446; hg19: chrM-8393;