Genetic Variant ATP5F1C:c.92-78C>T (chr10-7796969-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001001973.3(ATP5F1C):c.92-78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,506,596 control chromosomes in the GnomAD database, including 144,285 homozygotes. 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: 𝑓 0.44 ( 14706 hom., cov: 32)

Exomes 𝑓: 0.43 ( 129579 hom. )

Consequence

ATP5F1C
NM_001001973.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.68

Publications

9 publications found

Variant links:

Genes affected

ATP5F1C (HGNC:833): (ATP synthase F1 subunit gamma) 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 gamma subunit of the catalytic core. Alternatively spliced transcript variants encoding different isoforms have been identified. This gene also has a pseudogene on chromosome 14. [provided by RefSeq, Jul 2008]

ATP5F1C links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP5F1C	NM_001001973.3 link	c.92-78C>T		intron_variant	Intron 2 of 9	ENST00000356708.12	NP_001001973.1	P36542-1Q8TAS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP5F1C	ENST00000356708.12 link	c.92-78C>T		intron_variant	Intron 2 of 9	1	NM_001001973.3	ENSP00000349142.7		P36542-1

Frequencies

GnomAD3 genomes

AF:

0.438

AC:

66547

AN:

151920

Hom.:

14699

Cov.:

show subpopulations

Gnomad AFR

AF:

0.449

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.492

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.315

Gnomad SAS

AF:

0.553

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.434

Gnomad OTH

AF:

0.419

GnomAD4 exome

AF:

0.435

AC:

588631

AN:

1354560

Hom.:

129579

Cov.:

AF XY:

0.436

AC XY:

292243

AN XY:

669888

show subpopulations

African (AFR)

AF:

0.452

AC:

13535

AN:

29950

American (AMR)

AF:

0.557

AC:

19634

AN:

35254

Ashkenazi Jewish (ASJ)

AF:

0.416

AC:

9468

AN:

22756

East Asian (EAS)

AF:

0.326

AC:

12427

AN:

38154

South Asian (SAS)

AF:

0.539

AC:

40323

AN:

74768

European-Finnish (FIN)

AF:

0.367

AC:

18672

AN:

50810

Middle Eastern (MID)

AF:

0.425

AC:

2098

AN:

4938

European-Non Finnish (NFE)

AF:

0.430

AC:

447954

AN:

1041656

Other (OTH)

AF:

0.436

AC:

24520

AN:

56274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

15789

31577

47366

63154

78943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13938

27876

41814

55752

69690

<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:

0.438

AC:

66592

AN:

152036

Hom.:

14706

Cov.:

AF XY:

0.437

AC XY:

32462

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.449

AC:

18623

AN:

41456

American (AMR)

AF:

0.492

AC:

7517

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.411

AC:

1427

AN:

3470

East Asian (EAS)

AF:

0.315

AC:

1627

AN:

5170

South Asian (SAS)

AF:

0.552

AC:

2663

AN:

4824

European-Finnish (FIN)

AF:

0.378

AC:

3988

AN:

10562

Middle Eastern (MID)

AF:

0.435

AC:

127

AN:

292

European-Non Finnish (NFE)

AF:

0.434

AC:

29489

AN:

67960

Other (OTH)

AF:

0.418

AC:

884

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1965

3929

5894

7858

9823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.429

Hom.:

38200

Bravo

AF:

0.442

Asia WGS

AF:

0.470

AC:

1636

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.062

(source)

DANN

Benign

0.63

PhyloP100

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over