chr18-46084885-GT-G

Position:

• chr18-46084885-GT-G

Variant summary

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

The NM_004046.6(ATP5F1A):​c.1430-232del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 425,222 control chromosomes in the GnomAD database, including 4,374 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.099 (1041 hom., cov: 31)
  • Exomes 𝑓: 0.11 (3333 hom.)
• Consequence: ATP5F1A NM_004046.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0120

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 18-46084885-GT-G is Benign according to our data. Variant chr18-46084885-GT-G is described in ClinVar as [Benign]. Clinvar id is 1236688.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP5F1A	NM_004046.6	c.1430-232del		intron_variant		ENST00000398752.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP5F1A	ENST00000398752.11	c.1430-232del		intron_variant		1	NM_004046.6	P1

Frequencies

GnomAD3 genomes AF: 0.0990 AC: 15051 AN: 152016 Hom.: 1042 Cov.: 31

Gnomad AFR AF: 0.0809

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.0541

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0799

Gnomad OTH AF: 0.0922

GnomAD4 exome AF: 0.115 AC: 31399 AN: 273088 Hom.: 3333 Cov.: 3 AF XY: 0.113 AC XY: 15763 AN XY: 139820

Gnomad4 AFR exome AF: 0.0875

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.0944

Gnomad4 EAS exome AF: 0.454

Gnomad4 SAS exome AF: 0.0409

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.0802

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.0990 AC: 15061 AN: 152134 Hom.: 1041 Cov.: 31 AF XY: 0.102 AC XY: 7559 AN XY: 74354

Gnomad4 AFR AF: 0.0807

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.0545

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0800

Gnomad4 OTH AF: 0.0912

Alfa AF: 0.0281 Hom.: 20

Bravo AF: 0.106

Asia WGS AF: 0.206 AC: 715 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 29, 2018

- -

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: rs35503671; hg19: chr18-43664851;