10-7796969-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001973.3(ATP5F1C):c.92-78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,506,596 control chromosomes in the GnomAD database, including 144,285 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.44 (14706 hom., cov: 32)
  • Exomes 𝑓: 0.43 (129579 hom.)
• Consequence: ATP5F1C NM_001001973.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68

Genes affected

ATP5F1C (HGNC:833): (ATP synthase F1 subunit gamma) This gene encodes a subunit of mitochondrial ATP synthase. Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing 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 gamma subunit of the catalytic core. Alternatively spliced transcript variants encoding different isoforms have been identified. This gene also has a pseudogene on chromosome 14. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP5F1C	NM_001001973.3	c.92-78C>T		intron_variant		ENST00000356708.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP5F1C	ENST00000356708.12	c.92-78C>T		intron_variant		1	NM_001001973.3	P3

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66547 AN: 151920 Hom.: 14699 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.435 AC: 588631 AN: 1354560 Hom.: 129579 Cov.: 21 AF XY: 0.436 AC XY: 292243 AN XY: 669888

Gnomad4 AFR exome AF: 0.452

Gnomad4 AMR exome AF: 0.557

Gnomad4 ASJ exome AF: 0.416

Gnomad4 EAS exome AF: 0.326

Gnomad4 SAS exome AF: 0.539

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.436

GnomAD4 genome AF: 0.438 AC: 66592 AN: 152036 Hom.: 14706 Cov.: 32 AF XY: 0.437 AC XY: 32462 AN XY: 74330

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.315

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.418

Alfa AF: 0.423 Hom.: 22790

Bravo AF: 0.442

Asia WGS AF: 0.470 AC: 1636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.062
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1244422; hg19: chr10-7838932; COSMIC: COSV59621836; COSMIC: COSV59621836;