dbSNP rs1803181: ATP5PF:p.Pro106Leu (chr21-25724650-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001003703.2(ATP5PF):c.317C>T(p.Pro106Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,445,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ATP5PF
NM_001003703.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.20

Publications

0 publications found

Variant links:

Genes affected

ATP5PF (HGNC:847): (ATP synthase peripheral stalk subunit F6) Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. It is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, which comprises the proton channel. The F1 complex consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled in a ratio of 3 alpha, 3 beta, and a single representative of the other 3. The Fo complex has nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the F6 subunit of the Fo complex. The F6 subunit is required for F1 and Fo interactions. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. This gene has 1 or more pseudogenes. [provided by RefSeq, Feb 2016]

ATP5PF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27645636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP5PF	NM_001003703.2 link	c.317C>T	p.Pro106Leu	missense_variant	Exon 4 of 4	ENST00000284971.8	NP_001003703.1	P18859-1Q6IB54Q6NZ59

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP5PF	ENST00000284971.8 link	c.317C>T	p.Pro106Leu	missense_variant	Exon 4 of 4	1	NM_001003703.2	ENSP00000284971.3		P18859-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445062

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718816

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32078

American (AMR)

AF:

0.00

AC:

AN:

39460

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25754

East Asian (EAS)

AF:

0.00

AC:

AN:

38706

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82694

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107652

Other (OTH)

AF:

0.00

AC:

AN:

59694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

T;T;.;T;T;T

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.60

.;.;T;.;.;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.28

T;T;T;T;T;T

MetaSVM

Uncertain

-0.16

MutationAssessor

Uncertain

2.3

M;M;.;M;M;M

PhyloP100

4.2

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.5

D;D;D;D;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.012

D;D;D;D;D;D

Sift4G

Uncertain

0.016

D;D;D;D;D;D

Polyphen

1.0

D;D;.;D;D;D

Vest4

0.43

MutPred

0.36

Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);.;Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);Loss of sheet (P = 0.007);

MVP

0.45

MPC

0.58

ClinPred

0.92

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.078

gMVP

0.24

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over