chr1-111459542-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001688.5(ATP5PB):c.599A>G(p.His200Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ATP5PB
NM_001688.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.65

Publications

1 publications found

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]

ATP5PB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP5PB	NM_001688.5 link	c.599A>G	p.His200Arg	missense_variant	Exon 6 of 7	ENST00000369722.8	NP_001679.2	P24539Q08ET0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ATP5PB	ENST00000369722.8 link	c.599A>G	p.His200Arg	missense_variant	Exon 6 of 7	1	NM_001688.5	ENSP00000358737.3	P24539
ATP5PB	ENST00000483994.1 link	c.416A>G	p.His139Arg	missense_variant	Exon 4 of 5	2		ENSP00000420366.1	Q5QNZ2
ATP5PB	ENST00000369721.8 link	n.530A>G		non_coding_transcript_exon_variant	Exon 5 of 6	2
ATP5PB	ENST00000468818.1 link	n.369A>G		non_coding_transcript_exon_variant	Exon 5 of 6	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461642

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727132

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.0000224

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111830

Other (OTH)

AF:

0.0000166

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68050

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 13, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.599A>G (p.H200R) alteration is located in exon 6 (coding exon 6) of the ATP5F1 gene. This alteration results from a A to G substitution at nucleotide position 599, causing the histidine (H) at amino acid position 200 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

Uncertain

0.54

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

M;.

PhyloP100

8.6

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.7

D;N

REVEL

Benign

0.22

Sift

Uncertain

0.017

D;D

Sift4G

Uncertain

0.040

D;D

Polyphen

0.73

P;.

Vest4

0.48

MutPred

0.80

Gain of phosphorylation at S202 (P = 0.0738);.;

MVP

0.24

MPC

0.53

ClinPred

0.95

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.50

gMVP

0.65

Mutation Taster

=72/28

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

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chr1-111459542-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over