12-56639116-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001686.4(ATP5F1B):c.1479G>T(p.Gln493His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000579 in 1,614,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 1 hom. )

Consequence

ATP5F1B
NM_001686.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.427

Publications

3 publications found

Variant links:

Genes affected

ATP5F1B (HGNC:830): (ATP synthase F1 subunit beta) 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 beta subunit of the catalytic core. [provided by RefSeq, Jul 2008]

ATP5F1B Gene-Disease associations (from GenCC):

hypermetabolism due to uncoupled mitochondrial oxidative phosphorylation 2
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
mitochondrial proton-transporting ATP synthase complex deficiency
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ATP5F1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014221311).

BS2

High AC in GnomAd4 at 76 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001686.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP5F1B	NM_001686.4	MANE Select	c.1479G>T	p.Gln493His	missense	Exon 9 of 10	NP_001677.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP5F1B	ENST00000262030.8	TSL:1 MANE Select	c.1479G>T	p.Gln493His	missense	Exon 9 of 10	ENSP00000262030.3	P06576
ATP5F1B	ENST00000904666.1		c.1527G>T	p.Gln509His	missense	Exon 10 of 11	ENSP00000574725.1
ATP5F1B	ENST00000904670.1		c.1506G>T	p.Gln502His	missense	Exon 9 of 10	ENSP00000574729.1

Frequencies

GnomAD3 genomes

AF:

0.000499

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000605

AC:

152

AN:

251408

AF XY:

0.000596

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00466

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000853

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000588

AC:

859

AN:

1461848

Hom.:

Cov.:

AF XY:

0.000623

AC XY:

453

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33476

American (AMR)

AF:

0.0000671

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00482

AC:

126

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000169

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000600

AC:

667

AN:

1111994

Other (OTH)

AF:

0.000695

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

139

186

232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000499

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41564

American (AMR)

AF:

0.000261

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000764

AC:

AN:

68038

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000894

Hom.:

Bravo

AF:

0.000567

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000560

AC:

EpiCase

AF:

0.00125

EpiControl

AF:

0.00136

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Benign

0.11

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.85

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.053

MetaRNN

Benign

0.014

MetaSVM

Uncertain

-0.085

MutationAssessor

Benign

1.8

PhyloP100

0.43

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.97

REVEL

Benign

0.27

Sift

Benign

0.032

Sift4G

Uncertain

0.058

Polyphen

0.31

Vest4

0.34

MutPred

0.38

Gain of catalytic residue at Q492 (P = 0.0013)

MVP

0.59

MPC

0.018

ClinPred

0.037

GERP RS

3.9

Varity_R

0.089

gMVP

0.63

Mutation Taster

=79/21

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over