18-46084835-AAC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004046.6(ATP5F1A):c.1430-183_1430-182del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 569,314 control chromosomes in the GnomAD database, including 41,775 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (9031 hom., cov: 0)
  • Exomes 𝑓: 0.38 (32744 hom.)
• Consequence: ATP5F1A NM_004046.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.364

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 -10 ACMG points.

• BP6: Variant 18-46084835-AAC-A is Benign according to our data. Variant chr18-46084835-AAC-A is described in ClinVar as [Benign]. Clinvar id is 683338.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP5F1A	NM_004046.6	c.1430-183_1430-182del		intron_variant		ENST00000398752.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP5F1A	ENST00000398752.11	c.1430-183_1430-182del		intron_variant		1	NM_004046.6	P1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49315 AN: 151856 Hom.: 9037 Cov.: 0

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.0480

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.362

GnomAD4 exome AF: 0.379 AC: 158189 AN: 417338 Hom.: 32744 AF XY: 0.382 AC XY: 80846 AN XY: 211546

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.431

Gnomad4 EAS exome AF: 0.0307

Gnomad4 SAS exome AF: 0.420

Gnomad4 FIN exome AF: 0.373

Gnomad4 NFE exome AF: 0.418

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.324 AC: 49305 AN: 151976 Hom.: 9031 Cov.: 0 AF XY: 0.322 AC XY: 23929 AN XY: 74270

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.0479

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.360

Alfa AF: 0.359 Hom.: 1278

Bravo AF: 0.305

Asia WGS AF: 0.232 AC: 812 AN: 3478

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

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

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: rs33919884; hg19: chr18-43664801;