chrM-8545-G-A

Position:

• chrM-8545-G-A

Variant summary

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

The ENST00000361899.2(MT-ATP6):​c.19G>A​(p.Ala7Thr) 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 Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. A7A) has been classified as Likely benign.

• Frequency: Mitomap GenBank: 𝑓 0.0023 (AC: 141)
• Consequence: MT-ATP6 ENST00000361899.2 missense
• Scores: Apogee2 Benign 0.020
• Clinical Significance: Benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -0.162

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, 0.020404706 < 0.5 .
• BP6: Variant M-8545-G-A is Benign according to our data. Variant chrM-8545-G-A is described in ClinVar as [Benign]. Clinvar id is 692893.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 22

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6	ATP6.1	c.19G>A	p.Ala7Thr	missense_variant	1/1		YP_003024031.1
ATP8	ATP8.1	c.180G>A	p.Ser60=	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.19G>A	p.Ala7Thr	missense_variant	1/1			ENSP00000354632	P1
MT-ATP8	ENST00000361851.1	c.180G>A	p.Ser60=	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: 0.0023 AC: 141

Gnomad homoplasmic AF: 0.00039 AC: 22 AN: 56418

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56418

Alfa AF: 0.000445 Hom.: 2

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leigh syndrome Benign:1

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.8545G>A (YP_003024031.1:p.Ala7Thr) variant in MTATP6 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.020
Hmtvar	Benign	0.13
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.49	T
DEOGEN2	Benign	0.011	T
LIST_S2	Benign	0.50	T
MutationTaster	Benign	1.0	N;D
PROVEAN	Benign	0.22	N
Sift4G	Benign	0.26	T
GERP RS		-4.0
Varity_R		0.11

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1603221578; hg19: chrM-8546;