chr18-46084149-T-C

Position:

• chr18-46084149-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004046.6(ATP5F1A):​c.*133A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 675,934 control chromosomes in the GnomAD database, including 55,363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11704 hom., cov: 33)
  • Exomes 𝑓: 0.40 (43659 hom.)
• Consequence: ATP5F1A NM_004046.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 18-46084149-T-C is Benign according to our data. Variant chr18-46084149-T-C is described in ClinVar as [Benign]. Clinvar id is 1263382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP5F1A	NM_004046.6	c.*133A>G		3_prime_UTR_variant	12/12	ENST00000398752.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP5F1A	ENST00000398752.11	c.*133A>G		3_prime_UTR_variant	12/12	1	NM_004046.6	P1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58663 AN: 151998 Hom.: 11698 Cov.: 33

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.0620

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.396 AC: 207376 AN: 523818 Hom.: 43659 Cov.: 7 AF XY: 0.398 AC XY: 107638 AN XY: 270422

Gnomad4 AFR exome AF: 0.361

Gnomad4 AMR exome AF: 0.313

Gnomad4 ASJ exome AF: 0.459

Gnomad4 EAS exome AF: 0.0499

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.379

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.392

GnomAD4 genome AF: 0.386 AC: 58700 AN: 152116 Hom.: 11704 Cov.: 33 AF XY: 0.382 AC XY: 28394 AN XY: 74364

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.0619

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.406

Alfa AF: 0.417 Hom.: 12695

Bravo AF: 0.377

Asia WGS AF: 0.257 AC: 899 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 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.58

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: rs12954944; hg19: chr18-43664115;