ENST00000361851.1:c.17C>T

Variant names:

• chrM-8382-C-T
• rs1556423437
• ENST00000361851.1:c.17C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The ENST00000361851.1(MT-ATP8):​c.17C>T​(p.Thr6Ile) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T6S) has been classified as Uncertain significance.

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 9)
• Consequence: MT-ATP8 ENST00000361851.1 missense
• Scores: Apogee2 Benign 0.10
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2 Suspected-mito-disease
• Conservation: PhyloP100: 4.78
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.10092881 < 0.5 .

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-ATP8	ENST00000361851.1	TSL:6	c.17C>T	p.Thr6Ile	missense	Exon 1 of 1	ENSP00000355265.1
	MT-ATP6	ENST00000361899.2	TSL:6	c.-145C>T		upstream_gene	N/A	ENSP00000354632.2
	MT-CO2	ENST00000361739.1	TSL:6	c.*113C>T		downstream_gene	N/A	ENSP00000354876.1

Frequencies

Mitomap GenBank AF: 0.00010 AC: 9

Gnomad homoplasmic AF: 0.000053 AC: 3 AN: 56431

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56431

Alfa AF: 0.000223 Hom.: 1

Mitomap

Disease(s): Suspected-mito-disease

Status: Reported

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leigh syndrome Uncertain:1

Oct 17, 2019

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.8382C>T (YP_003024030.1:p.Thr6Ile) variant in MTATP8 gene is interpretated to be a Uncertain Significance variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: PP6

not provided Uncertain:1

May 30, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.10
Hmtvar	Pathogenic	0.77
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.28	T
DEOGEN2	Benign	0.24	T
LIST_S2	Benign	0.79	T
PhyloP100		4.8
PROVEAN	Pathogenic	-5.0	D
Sift	Benign	0.043	D
Sift4G	Uncertain	0.049	D
GERP RS		4.0
Varity_R		0.22

Other links and lift over

dbSNP: rs1556423437; hg19: chrM-8383;