rs1057520079
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4BP6_Very_StrongBS2
The ENST00000361899.2(MT-ATP6):c.565A>G(p.Thr189Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Mitomap GenBank:
𝑓 0.00030 ( AC: 20 )
Consequence
MT-ATP6
ENST00000361899.2 missense
ENST00000361899.2 missense
Scores
Apogee2
Benign
Clinical Significance
No linked disesase in Mitomap
Conservation
PhyloP100: 0.419
Genes affected
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Apogee2 supports a benign effect, 0.006389093 < 0.5 .
BP6
?
Variant M-9091-A-G is Benign according to our data. Variant chrM-9091-A-G is described in ClinVar as [Benign]. Clinvar id is 376876.Status of the report is reviewed_by_expert_panel, 3 stars.
BS2
?
High AC in GnomadMitoHomoplasmic at 20
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP6 | ATP6.1 use as main transcript | c.565A>G | p.Thr189Ala | missense_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MT-ATP6 | ENST00000361899.2 | c.565A>G | p.Thr189Ala | missense_variant | 1/1 | P1 |
Frequencies
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
We have no GnomAD4 genomes data on this position. Probably position not covered by the project.
Mitomap GenBank
AF:
AC:
20
Gnomad homoplasmic
AF:
AC:
20
AN:
56432
Gnomad heteroplasmic
AF:
AC:
0
AN:
56432
Mitomap
No disease associated.
ClinVar
Significance: Benign
Submissions summary: Uncertain:1Benign:2
Revision: reviewed by expert panel
LINK: link
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 | Jan 16, 2017 | - - |
Mitochondrial disease Benign:1
Benign, reviewed by expert panel | curation | ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen | Jun 26, 2023 | The m.9091A>G (p.T189A) variant in MT-ATP6 was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel on June 26, 2023. This variant has not been reported in the medical literature as causative in affected individuals or families with primary mitochondrial disease to our knowledge. There has been a report of this variant being present in an individual from a control cohort (PMID: 15120634). This variant has also been reported in the homoplasmic state in a family with Leber Hereditary Optic Neuropathy (from haplogroup H10) caused by the m.3733G>A variant (PMID: 22879922). There are several occurrences in population databases. The frequency in the MITOMAP GenBank sequences is 21/59,389 (0.035%). The frequency in the Helix dataset is 108/195,983 (0.055%), including 107 homoplasmic occurrences and 1 heteroplasmic occurrence, and occurring in individuals from haplogroups H, U, HV, K, and R. The frequency in gnomAD v3.1.2 is 20/56432 (0.035%), and these occurrences are homoplasmic in individuals of European and African ancestry. Furthermore, this variant has been reported in 14 out of 14 individuals in the H10 haplogroup in addition to the case described above in haplogroup H10, meeting criteria to be considered a top-level haplogroup defining variant (BA1). The computational predictor APOGEE gives a consensus rating of benign with a score of 0.28 (Min=0, Max=1), which predicts a benign effect on gene function (BP4). There are no cybrids, single fiber studies, or other functional assays reported on this variant. In summary, this variant meets criteria to be classified as benign for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Variant Curation Expert Panel on June 26, 2023. Mitochondrial DNA-specific ACMG/AMP criteria applied BP4, BA1. - |
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.9091A>G (YP_003024031.1:p.Thr189Ala) 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, BP4 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Apogee2
Benign
Hmtvar
Benign
AlphaMissense
Benign
BayesDel_addAF
Benign
T
DEOGEN2
Benign
T
LIST_S2
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PROVEAN
Benign
N
Sift4G
Benign
T
GERP RS
Varity_R
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at