18-46083996-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.72

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]

ACMG classification

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	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	c.*286G>T		3_prime_UTR_variant	12/12	1	NM_004046.6	P1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 79034 AN: 139256 Hom.: 22313 Cov.: 26

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.: 0 AF XY: 0.287 AC XY: 4272 AN XY: 14872

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.: 26 AF XY: 0.562 AC XY: 37718 AN XY: 67164

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.: 30

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 11, 2019

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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

Other links and lift over

dbSNP: rs2578195; hg19: chr18-43663962;