rs587776444

chrM-8989-G-AchrM-8989-G-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM1 BP4 BP6_Moderate BS2

The ENST00000361899.2(MT-ATP6):c.463G>A(p.Ala155Thr) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Mitomap GenBank: 𝑓 0.00060 (AC: 35)
• Consequence: MT-ATP6 ENST00000361899.2 missense
• Scores: Apogee2 Benign 0.10
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 7.78

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM1: In a transmembrane_region Helical (size 20) in uniprot entity ATP6_HUMAN there are 6 pathogenic changes around while only 1 benign (86%) in ENST00000361899.2
• BP4: Apogee2 supports a benign effect, 0.10180157 < 0.5 .
• BP6: Variant M-8989-G-A is Benign according to our data. Variant chrM-8989-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 693046.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 13

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6	ATP6.1	c.463G>A	p.Ala155Thr	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MT-ATP6	ENST00000361899.2	c.463G>A	p.Ala155Thr	missense_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: 0.00060 AC: 35

Gnomad homoplasmic AF: 0.00023 AC: 13 AN: 56415

Gnomad heteroplasmic AF: 0.00011 AC: 6 AN: 56415

Alfa AF: 0.000111 Hom.: 0

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.8989G>A (YP_003024031.1:p.Ala155Thr) 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	0.10
Hmtvar	Pathogenic	0.74
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.15	D
DEOGEN2	Benign	0.071	T
LIST_S2	Benign	0.78	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	D
PROVEAN	Uncertain	-3.2	D
Sift4G	Uncertain	0.018	D
GERP RS		4.1
Varity_R		0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs587776444; hg19: chrM-8990;