X-40606113-A-G

Variant summary

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

The NM_005765.3(ATP6AP2):c.*358A>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 0.0389 in 196,742 control chromosomes in the GnomAD database, including 412 homozygotes. There are 2,214 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 0.049 (291 hom., 1662 hem., cov: 23)
  • Exomes 𝑓: 0.025 (121 hom. 552 hem.)
• Consequence: ATP6AP2 NM_005765.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6AP2	NM_005765.3	c.*358A>G		3_prime_UTR_variant	9/9	ENST00000636580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6AP2	ENST00000636580.2	c.*358A>G		3_prime_UTR_variant	9/9	1	NM_005765.3	P3

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 5548 AN: 112394 Hom.: 290 Cov.: 23 AF XY: 0.0480 AC XY: 1657 AN XY: 34546

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.00339

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.00864

Gnomad FIN AF: 0.00195

Gnomad MID AF: 0.0210

Gnomad NFE AF: 0.00161

Gnomad OTH AF: 0.0549

GnomAD4 exome AF: 0.0250 AC: 2106 AN: 84293 Hom.: 121 Cov.: 0 AF XY: 0.0278 AC XY: 552 AN XY: 19875

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.208

Gnomad4 ASJ exome AF: 0.00217

Gnomad4 EAS exome AF: 0.196

Gnomad4 SAS exome AF: 0.00914

Gnomad4 FIN exome AF: 0.00295

Gnomad4 NFE exome AF: 0.00142

Gnomad4 OTH exome AF: 0.0280

GnomAD4 genome AF: 0.0494 AC: 5554 AN: 112449 Hom.: 291 Cov.: 23 AF XY: 0.0480 AC XY: 1662 AN XY: 34611

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.00339

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.00830

Gnomad4 FIN AF: 0.00195

Gnomad4 NFE AF: 0.00161

Gnomad4 OTH AF: 0.0542

Alfa AF: 0.0158 Hom.: 269

Bravo AF: 0.0682

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.9
Dann	Benign	0.59

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: rs6609080; hg19: chrX-40465365; COSMIC: COSV65798465; COSMIC: COSV65798465;