1-111454212-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001688.5(ATP5PB):​c.79G>T​(p.Val27Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000945 in 1,587,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

ATP5PB
NM_001688.5 missense, splice_region

Scores

1
18
Splicing: ADA: 0.0001531
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.12
Variant links:
Genes affected
ATP5PB (HGNC:840): (ATP synthase peripheral stalk-membrane subunit b) 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 seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the b subunit of the proton channel. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04027021).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATP5PBNM_001688.5 linkuse as main transcriptc.79G>T p.Val27Leu missense_variant, splice_region_variant 3/7 ENST00000369722.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATP5PBENST00000369722.8 linkuse as main transcriptc.79G>T p.Val27Leu missense_variant, splice_region_variant 3/71 NM_001688.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152150
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
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:
0.0000311
AC:
7
AN:
225196
Hom.:
0
AF XY:
0.0000246
AC XY:
3
AN XY:
121958
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000410
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:
0.00000767
AC:
11
AN:
1435024
Hom.:
0
Cov.:
30
AF XY:
0.00000701
AC XY:
5
AN XY:
713546
show subpopulations
Gnomad4 AFR exome
AF:
0.0000312
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000229
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152150
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 21, 2023The c.79G>T (p.V27L) alteration is located in exon 3 (coding exon 3) of the ATP5F1 gene. This alteration results from a G to T substitution at nucleotide position 79, causing the valine (V) at amino acid position 27 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
15
DANN
Benign
0.59
DEOGEN2
Benign
0.025
T
Eigen
Benign
-0.94
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.36
N
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.040
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
0.88
L
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-0.88
N
REVEL
Benign
0.018
Sift
Benign
0.41
T
Sift4G
Benign
0.82
T
Polyphen
0.039
B
Vest4
0.23
MutPred
0.39
Gain of glycosylation at P25 (P = 0.146);
MVP
0.092
MPC
0.18
ClinPred
0.024
T
GERP RS
2.9
Varity_R
0.052
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00015
dbscSNV1_RF
Benign
0.0
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: rs770878179; hg19: chr1-111996834; API