chr1-111460927-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001688.5(ATP5PB):ā€‹c.704C>Gā€‹(p.Thr235Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

ATP5PB
NM_001688.5 missense

Scores

3
9
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.29
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36822042).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATP5PBNM_001688.5 linkuse as main transcriptc.704C>G p.Thr235Arg missense_variant 7/7 ENST00000369722.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATP5PBENST00000369722.8 linkuse as main transcriptc.704C>G p.Thr235Arg missense_variant 7/71 NM_001688.5 P1
ATP5PBENST00000483994.1 linkuse as main transcriptc.521C>G p.Thr174Arg missense_variant 5/52
ATP5PBENST00000369721.8 linkuse as main transcriptn.635C>G non_coding_transcript_exon_variant 6/62
ATP5PBENST00000468818.1 linkuse as main transcriptn.474C>G non_coding_transcript_exon_variant 6/63

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.000478
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152170
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.000478

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 GeneticsMar 28, 2022The c.704C>G (p.T235R) alteration is located in exon 7 (coding exon 7) of the ATP5F1 gene. This alteration results from a C to G substitution at nucleotide position 704, causing the threonine (T) at amino acid position 235 to be replaced by an arginine (R). 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
Pathogenic
0.61
BayesDel_addAF
Uncertain
0.031
T
BayesDel_noAF
Benign
-0.19
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;.
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.37
T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Uncertain
2.9
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-2.8
D;D
REVEL
Benign
0.19
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
0.99
D;.
Vest4
0.39
MutPred
0.53
Gain of MoRF binding (P = 0.0075);.;
MVP
0.42
MPC
0.79
ClinPred
0.98
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.93
gMVP
0.56

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: rs1317681359; hg19: chr1-112003549; API