M-8565-A-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The ENST00000361851.1(MT-ATP8):c.200A>G(p.Gln67Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Mitomap GenBank: 𝑓 0.00010 (AC: 5)
• Consequence: MT-ATP8 ENST00000361851.1 missense
• Scores: Apogee2 Benign 0.13
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.795

Genes affected

ATP8 (HGNC:):

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.12685725 < 0.5 .
• BS2: High AC in GnomadMitoHomoplasmic at 4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8	ATP8.1	c.200A>G	p.Gln67Arg	missense_variant	1/1
ATP6	ATP6.1	c.39A>G	p.Thr13=	synonymous_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-ATP8	ENST00000361851.1	c.200A>G	p.Gln67Arg	missense_variant	1/1			P1
MT-ATP6	ENST00000361899.2	c.39A>G	p.Thr13=	synonymous_variant	1/1			P1

Frequencies

GnomAD4 exome Cov.: 0

We have no GnomAD4 genomes data on this position. Probably position not covered by the project.

Mitomap GenBank AF: 0.00010 AC: 5

Gnomad homoplasmic AF: 0.000071 AC: 4 AN: 56433

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56433

Mitomap

No disease associated.

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

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

Oct 09, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.13
Hmtvar	Benign	0.14
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.36	T
DEOGEN2	Benign	0.082	T
LIST_S2	Benign	0.67	T
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	-2.2	N
Sift	Benign	0.030	D
Sift4G	Uncertain	0.041	D
GERP RS		2.1
Varity_R		0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs878853052; hg19: chrM-8566;