Genetic Variant ATP5F1B:p.Ala59Thr (chr12-56645306-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001686.4(ATP5F1B):c.175G>A(p.Ala59Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Consequence

ATP5F1B
NM_001686.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.786

Publications

1 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 links:

SNORD59A (HGNC:10210): (small nucleolar RNA, C/D box 59A)

SNORD59A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12036005).

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.175G>A	p.Ala59Thr	missense	Exon 2 of 10	NP_001677.2
	SNORD59A	NR_002737.1		n.-205G>A		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP5F1B	ENST00000262030.8	TSL:1 MANE Select	c.175G>A	p.Ala59Thr	missense	Exon 2 of 10	ENSP00000262030.3	P06576
ATP5F1B	ENST00000904666.1		c.175G>A	p.Ala59Thr	missense	Exon 2 of 11	ENSP00000574725.1
ATP5F1B	ENST00000904670.1		c.202G>A	p.Ala68Thr	missense	Exon 2 of 10	ENSP00000574729.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

251318

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

0.079

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.11

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.82

M_CAP

Benign

0.033

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.81

PhyloP100

0.79

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.45

REVEL

Benign

0.11

Sift

Benign

0.089

Sift4G

Benign

0.15

Polyphen

0.015

Vest4

0.091

MutPred

0.28

Gain of catalytic residue at T60 (P = 0.0012)

MVP

0.60

MPC

1.2

ClinPred

0.72

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.059

gMVP

0.37

Mutation Taster

=51/49

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over