chr1-111460990-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001688.5(ATP5PB):ā€‹c.767T>Cā€‹(p.Met256Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ATP5PB
NM_001688.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14483726).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATP5PBNM_001688.5 linkuse as main transcriptc.767T>C p.Met256Thr missense_variant 7/7 ENST00000369722.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATP5PBENST00000369722.8 linkuse as main transcriptc.767T>C p.Met256Thr missense_variant 7/71 NM_001688.5 P1
ATP5PBENST00000483994.1 linkuse as main transcriptc.584T>C p.Met195Thr missense_variant 5/52
ATP5PBENST00000369721.8 linkuse as main transcriptn.698T>C non_coding_transcript_exon_variant 6/62
ATP5PBENST00000468818.1 linkuse as main transcriptn.537T>C non_coding_transcript_exon_variant 6/63

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000137
AC:
2
AN:
1459638
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726128
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 GeneticsDec 16, 2023The c.767T>C (p.M256T) alteration is located in exon 7 (coding exon 7) of the ATP5F1 gene. This alteration results from a T to C substitution at nucleotide position 767, causing the methionine (M) at amino acid position 256 to be replaced by a threonine (T). 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
0.23
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
21
DANN
Benign
0.90
DEOGEN2
Benign
0.019
T;.
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.016
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.66
T;T
M_CAP
Benign
0.0059
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;.
MutationTaster
Benign
0.83
N;N
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-0.57
N;N
REVEL
Benign
0.051
Sift
Uncertain
0.0050
D;D
Sift4G
Uncertain
0.023
D;D
Polyphen
0.094
B;.
Vest4
0.20
MutPred
0.56
Gain of glycosylation at M256 (P = 0.0242);.;
MVP
0.13
MPC
0.23
ClinPred
0.37
T
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.36
gMVP
0.43

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: rs1653607284; hg19: chr1-112003612; API