chrM-8530-A-G

Position:

• chrM-8530-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000361899.2(MT-ATP6):​c.4A>G​(p.Asn2Asp) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N2S) has been classified as Likely benign.

• Frequency: Mitomap GenBank: 𝑓 0.00020 (AC: 13)
• Consequence: MT-ATP6 ENST00000361899.2 missense
• Scores: Apogee2 Benign 0.077
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 7.10

Genes affected

ATP6 (HGNC:):

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-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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.077158935 < 0.5 .
• BP6: Variant M-8530-A-G is Benign according to our data. Variant chrM-8530-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 692887.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 15

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6	ATP6.1	c.4A>G	p.Asn2Asp	missense_variant	1/1		YP_003024031.1
ATP8	ATP8.1	c.165A>G	p.Trp55=	synonymous_variant	1/1		YP_003024030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-ATP6	ENST00000361899.2	c.4A>G	p.Asn2Asp	missense_variant	1/1			ENSP00000354632	P1
MT-ATP8	ENST00000361851.1	c.165A>G	p.Trp55=	synonymous_variant	1/1			ENSP00000355265	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: 0.00020 AC: 13

Gnomad homoplasmic AF: 0.00027 AC: 15 AN: 56432

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56432

Alfa AF: 0.00134 Hom.: 6

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

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

Oct 17, 2019

The NC_012920.1:m.8530A>G (YP_003024031.1:p.Asn2Asp) variant in MTATP6 gene is interpretated to be a Likely Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BP6 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.077
Hmtvar	Pathogenic	0.64
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.032	T
DEOGEN2	Benign	0.085	T
LIST_S2	Benign	0.76	T
MutationTaster	Benign	1.0	D;D
PROVEAN	Uncertain	-3.1	D
Sift4G	Uncertain	0.015	D
GERP RS		5.1
Varity_R		0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1556423480; hg19: chrM-8531;