chrM-8417-C-T

Variant names:

• chrM-8417-C-T
• rs199616772
• ENST00000361851.1:c.52C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000361851.1(MT-ATP8):​c.52C>T​(p.Leu18Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L18P) has been classified as Uncertain significance.

• Frequency: Mitomap GenBank: 𝑓 0.00080 (AC: 47)
• Consequence: MT-ATP8 ENST00000361851.1 missense
• Scores: Apogee2 Benign 0.090
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -20.0
• Publications: 3 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 -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.08969416 < 0.5 .
• BP6: Variant M-8417-C-T is Benign according to our data. Variant chrM-8417-C-T is described in ClinVar as Benign. ClinVar VariationId is 692852.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 91

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361851.1. 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-ATP8	ENST00000361851.1	TSL:6	c.52C>T	p.Leu18Phe	missense	Exon 1 of 1	ENSP00000355265.1	P03928
	MT-ATP6	ENST00000361899.2	TSL:6	c.-110C>T		upstream_gene	N/A	ENSP00000354632.2	P00846
	MT-CO2	ENST00000361739.1	TSL:6	c.*148C>T		downstream_gene	N/A	ENSP00000354876.1	P00403

Frequencies

Mitomap GenBank AF: 0.00080 AC: 47

Gnomad homoplasmic AF: 0.0016 AC: 91 AN: 56432

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56432

Alfa AF: 0.000860 Hom.: 40

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.090
Hmtvar	Pathogenic	0.71
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.42	T
DEOGEN2	Benign	0.081	T
LIST_S2	Benign	0.67	T
PhyloP100		-20
PROVEAN	Uncertain	-2.9	D
Sift	Uncertain	0.014	D
Sift4G	Benign	0.071	T
GERP RS		-9.6
Varity_R		0.34

Other links and lift over

dbSNP: rs199616772; hg19: chrM-8418;