rs4655

Positions:

• chr10-7807725-T-C
• chr10-7807725-T-G

Variant summary

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

The NM_001001973.3(ATP5F1C):​c.*97T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 1,557,388 control chromosomes in the GnomAD database, including 103,286 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 0.35 (9230 hom., cov: 32)
  • Exomes 𝑓: 0.36 (94056 hom.)
• Consequence: ATP5F1C NM_001001973.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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]

LOC105376392 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• 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	Protein	UniProt
ATP5F1C	NM_001001973.3	c.*97T>C		3_prime_UTR_variant	10/10	ENST00000356708.12	NP_001001973.1
LOC105376392	XR_001747356.1	n.191+739A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP5F1C	ENST00000356708.12	c.*97T>C		3_prime_UTR_variant	10/10	1	NM_001001973.3	ENSP00000349142	P3

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52876 AN: 151980 Hom.: 9230 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.327

GnomAD4 exome AF: 0.364 AC: 512211 AN: 1405290 Hom.: 94056 Cov.: 25 AF XY: 0.365 AC XY: 255610 AN XY: 699756

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.368

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.259

Gnomad4 SAS exome AF: 0.426

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.360

GnomAD4 genome AF: 0.348 AC: 52902 AN: 152098 Hom.: 9230 Cov.: 32 AF XY: 0.347 AC XY: 25832 AN XY: 74358

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.327

Alfa AF: 0.351 Hom.: 15816

Bravo AF: 0.340

Asia WGS AF: 0.369 AC: 1283 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.8
DANN	Benign	0.81
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: rs4655; hg19: chr10-7849688; COSMIC: COSV59621724;