20-59030421-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006886.4(ATP5F1E):​c.41G>A​(p.Arg14Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,613,560 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R14P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ATP5F1E
NM_006886.4 missense

Scores

5
7
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.66
Variant links:
Genes affected
ATP5F1E (HGNC:838): (ATP synthase F1 subunit epsilon) This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing 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 epsilon subunit of the catalytic core. Two pseudogenes of this gene are located on chromosomes 4 and 13. Read-through transcripts that include exons from this gene are expressed from the upstream gene SLMO2.[provided by RefSeq, Mar 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATP5F1ENM_006886.4 linkc.41G>A p.Arg14Gln missense_variant Exon 2 of 3 ENST00000243997.8 NP_008817.1 P56381
SLMO2-ATP5ENR_037929.1 linkn.745G>A non_coding_transcript_exon_variant Exon 7 of 8
SLMO2-ATP5ENR_037930.1 linkn.486G>A non_coding_transcript_exon_variant Exon 5 of 6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATP5F1EENST00000243997.8 linkc.41G>A p.Arg14Gln missense_variant Exon 2 of 3 1 NM_006886.4 ENSP00000243997.3 P56381
ATP5F1EENST00000395659.1 linkc.41G>A p.Arg14Gln missense_variant Exon 2 of 2 1 ENSP00000379019.1 P56381
ATP5F1EENST00000395663.1 linkc.41G>A p.Arg14Gln missense_variant Exon 2 of 3 2 ENSP00000379023.1 P56381

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152156
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251422
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461404
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727020
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152156
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.0000966
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.34
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Pathogenic
0.19
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.21
T;T;T
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.87
.;.;D
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.59
D;D;D
MetaSVM
Uncertain
-0.15
T
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-0.39
N;N;N
REVEL
Uncertain
0.44
Sift
Benign
0.082
T;T;T
Sift4G
Benign
0.18
T;T;T
Polyphen
1.0
D;D;D
Vest4
0.73
MutPred
0.54
Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);Loss of MoRF binding (P = 0.015);
MVP
0.83
MPC
0.080
ClinPred
0.74
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.16
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs138025844; hg19: chr20-57605476; COSMIC: COSV53885771; COSMIC: COSV53885771; API