Variant chr18-46083996-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004046.6(ATP5F1A):c.*286G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 167,914 control chromosomes in the GnomAD database, including 23,497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.57 ( 22321 hom., cov: 26)

Exomes 𝑓: 0.28 ( 1176 hom. )

Consequence

ATP5F1A
NM_004046.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.72

Variant links:

Genes affected

ATP5F1A (HGNC:823): (ATP synthase F1 subunit alpha) This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, using 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 alpha subunit of the catalytic core. Alternatively spliced transcript variants encoding the different isoforms have been identified. Pseudogenes of this gene are located on chromosomes 9, 2, and 16. [provided by RefSeq, Mar 2012]

ATP5F1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 18-46083996-C-A is Benign according to our data. Variant chr18-46083996-C-A is described in ClinVar as [Benign]. Clinvar id is 1255357.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP5F1A	NM_004046.6 linkuse as main transcript	c.*286G>T		3_prime_UTR_variant	12/12	ENST00000398752.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP5F1A	ENST00000398752.11 linkuse as main transcript	c.*286G>T		3_prime_UTR_variant	12/12	1	NM_004046.6	P1	P25705-1

Frequencies

GnomAD3 genomes

AF:

0.568

AC:

79034

AN:

139256

Hom.:

22313

Cov.:

show subpopulations

Gnomad AFR

AF:

0.649

Gnomad AMI

AF:

0.532

Gnomad AMR

AF:

0.513

Gnomad ASJ

AF:

0.588

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.516

Gnomad FIN

AF:

0.487

Gnomad MID

AF:

0.631

Gnomad NFE

AF:

0.556

Gnomad OTH

AF:

0.568

GnomAD4 exome

AF:

0.284

AC:

8126

AN:

28618

Hom.:

1176

Cov.:

AF XY:

0.287

AC XY:

4272

AN XY:

14872

show subpopulations

Gnomad4 AFR exome

AF:

0.411

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.304

Gnomad4 EAS exome

AF:

0.223

Gnomad4 SAS exome

AF:

0.280

Gnomad4 FIN exome

AF:

0.253

Gnomad4 NFE exome

AF:

0.289

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.568

AC:

79058

AN:

139296

Hom.:

22321

Cov.:

AF XY:

0.562

AC XY:

37718

AN XY:

67164

show subpopulations

Gnomad4 AFR

AF:

0.649

Gnomad4 AMR

AF:

0.513

Gnomad4 ASJ

AF:

0.588

Gnomad4 EAS

AF:

0.442

Gnomad4 SAS

AF:

0.515

Gnomad4 FIN

AF:

0.487

Gnomad4 NFE

AF:

0.556

Gnomad4 OTH

AF:

0.565

Alfa

AF:

0.0155

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.70

DANN

Benign

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over