rs141639003
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_004046.6(ATP5F1A):c.25G>A(p.Ala9Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000514 in 1,607,002 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00046 ( 10 hom. )
Consequence
ATP5F1A
NM_004046.6 missense
NM_004046.6 missense
Scores
3
13
Clinical Significance
Conservation
PhyloP100: 3.97
Genes affected
ATP5F1A (HGNC:823): (ATP synthase F1 subunit alpha) This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, using an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. ATP synthase is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, comprising the proton channel. The catalytic portion of mitochondrial ATP synthase consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled with a stoichiometry of 3 alpha, 3 beta, and a single representative of the other 3. The proton channel consists of three main subunits (a, b, c). This gene encodes the alpha subunit of the catalytic core. Alternatively spliced transcript variants encoding the different isoforms have been identified. Pseudogenes of this gene are located on chromosomes 9, 2, and 16. [provided by RefSeq, Mar 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, ATP5F1A
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008045375).
BP6
?
Variant 18-46098207-C-T is Benign according to our data. Variant chr18-46098207-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00105 (160/152348) while in subpopulation AMR AF= 0.00764 (117/15308). AF 95% confidence interval is 0.00652. There are 1 homozygotes in gnomad4. There are 74 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 10 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP5F1A | NM_004046.6 | c.25G>A | p.Ala9Thr | missense_variant | 1/12 | ENST00000398752.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP5F1A | ENST00000398752.11 | c.25G>A | p.Ala9Thr | missense_variant | 1/12 | 1 | NM_004046.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00104 AC: 159AN: 152230Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00205 AC: 487AN: 237102Hom.: 8 AF XY: 0.00140 AC XY: 183AN XY: 130732
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GnomAD4 exome AF: 0.000458 AC: 666AN: 1454654Hom.: 10 Cov.: 39 AF XY: 0.000361 AC XY: 261AN XY: 723768
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GnomAD4 genome ? AF: 0.00105 AC: 160AN: 152348Hom.: 1 Cov.: 32 AF XY: 0.000993 AC XY: 74AN XY: 74500
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Uncertain:1Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 17, 2017 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 11, 2016 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 15, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
ATP5F1A-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 29, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;.;.
REVEL
Benign
Sift
Benign
T;T;.;.;.
Sift4G
Benign
T;T;T;.;.
Polyphen
B;B;.;.;.
Vest4
MVP
MPC
0.29
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at