18-46083995-AC-A

Variant names:

• chr18-46083995-AC-A
• rs202210184
• NM_004046.6:c.*286delG

Variant summary

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

The NM_004046.6(ATP5F1A):​c.*286delG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 196,366 control chromosomes in the GnomAD database, including 133 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (128 hom., cov: 26)
  • Exomes 𝑓: 0.014 (5 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 -10 ACMG points.

• BP6: Variant 18-46083995-AC-A is Benign according to our data. Variant chr18-46083995-AC-A is described in ClinVar as [Benign]. Clinvar id is 1239941.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP5F1A	NM_004046.6	c.*286delG		3_prime_UTR_variant	Exon 12 of 12	ENST00000398752.11	NP_004037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP5F1A	ENST00000398752	c.*286delG		3_prime_UTR_variant	Exon 12 of 12	1	NM_004046.6	ENSP00000381736.5

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2438 AN: 148592 Hom.: 128 Cov.: 26

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00908

Gnomad FIN AF: 0.00169

Gnomad MID AF: 0.0131

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.0119

GnomAD4 exome AF: 0.0137 AC: 654 AN: 47676 Hom.: 5 Cov.: 0 AF XY: 0.0136 AC XY: 335 AN XY: 24678

Gnomad4 AFR exome AF: 0.0275

Gnomad4 AMR exome AF: 0.0142

Gnomad4 ASJ exome AF: 0.0150

Gnomad4 EAS exome AF: 0.00302

Gnomad4 SAS exome AF: 0.0238

Gnomad4 FIN exome AF: 0.0134

Gnomad4 NFE exome AF: 0.0135

Gnomad4 OTH exome AF: 0.0162

GnomAD4 genome AF: 0.0164 AC: 2441 AN: 148690 Hom.: 128 Cov.: 26 AF XY: 0.0156 AC XY: 1131 AN XY: 72562

Gnomad4 AFR AF: 0.0547

Gnomad4 AMR AF: 0.00555

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00888

Gnomad4 FIN AF: 0.00169

Gnomad4 NFE AF: 0.00134

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.000462 Hom.: 0

Asia WGS AF: 0.00843 AC: 29 AN: 3454

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 15, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: rs202210184; hg19: chr18-43663961;