rs1060063

Positions:

• chrX-40606564-T-C

Variant summary

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

The NM_005765.3(ATP6AP2):​c.*809T>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 0.145 in 111,842 control chromosomes in the GnomAD database, including 2,279 homozygotes. There are 4,610 hemizygotes in GnomAD. 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 0.14 (2279 hom., 4610 hem., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ATP6AP2 NM_005765.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

Genes affected

ATP6AP2 (HGNC:18305): (ATPase H+ transporting accessory protein 2) This gene encodes a protein that is associated with adenosine triphosphatases (ATPases). Proton-translocating ATPases have fundamental roles in energy conservation, secondary active transport, acidification of intracellular compartments, and cellular pH homeostasis. There are three classes of ATPases- F, P, and V. The vacuolar (V-type) ATPases have a transmembrane proton-conducting sector and an extramembrane catalytic sector. The encoded protein has been found associated with the transmembrane sector of the V-type ATPases. [provided by RefSeq, Jul 2008]

ATP6AP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6AP2	NM_005765.3	c.*809T>C		3_prime_UTR_variant	9/9	ENST00000636580.2	NP_005756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6AP2	ENST00000636580.2	c.*809T>C		3_prime_UTR_variant	9/9	1	NM_005765.3	ENSP00000490083.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 16158 AN: 111789 Hom.: 2279 Cov.: 23 AF XY: 0.135 AC XY: 4587 AN XY: 33999

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0175

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.0502

Gnomad NFE AF: 0.00586

Gnomad OTH AF: 0.140

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 302 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 130

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.145 AC: 16180 AN: 111842 Hom.: 2279 Cov.: 23 AF XY: 0.135 AC XY: 4610 AN XY: 34062

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.00424

Gnomad4 NFE AF: 0.00586

Gnomad4 OTH AF: 0.138

Alfa AF: 0.0717 Hom.: 761

Bravo AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.6
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: rs1060063; hg19: chrX-40465816;