X-40581020-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005765.3(ATP6AP2):c.-46C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000464 in 1,160,049 control chromosomes in the GnomAD database, including 1 homozygotes. There are 145 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., 72 hem., cov: 25)
  • Exomes 𝑓: 0.00025 (1 hom. 73 hem.)
• Consequence: ATP6AP2 NM_005765.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.977

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant X-40581020-C-A is Benign according to our data. Variant chrX-40581020-C-A is described in ClinVar as [Benign]. Clinvar id is 204913.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 72 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6AP2	NM_005765.3	c.-46C>A		5_prime_UTR_variant	1/9	ENST00000636580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6AP2	ENST00000636580.2	c.-46C>A		5_prime_UTR_variant	1/9	1	NM_005765.3	P3

Frequencies

GnomAD3 genomes AF: 0.00245 AC: 278 AN: 113286 Hom.: 0 Cov.: 25 AF XY: 0.00203 AC XY: 72 AN XY: 35436

Gnomad AFR AF: 0.00806

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00193

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00262

GnomAD3 exomes AF: 0.000534 AC: 55 AN: 103015 Hom.: 0 AF XY: 0.000543 AC XY: 20 AN XY: 36835

Gnomad AFR exome AF: 0.00703

Gnomad AMR exome AF: 0.000726

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000269

Gnomad OTH exome AF: 0.000648

GnomAD4 exome AF: 0.000249 AC: 261 AN: 1046714 Hom.: 1 Cov.: 29 AF XY: 0.000215 AC XY: 73 AN XY: 339844

Gnomad4 AFR exome AF: 0.00795

Gnomad4 AMR exome AF: 0.000790

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000201

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000736

Gnomad4 OTH exome AF: 0.000725

GnomAD4 genome AF: 0.00244 AC: 277 AN: 113335 Hom.: 0 Cov.: 25 AF XY: 0.00203 AC XY: 72 AN XY: 35495

Gnomad4 AFR AF: 0.00801

Gnomad4 AMR AF: 0.00193

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00258

Alfa AF: 0.00152 Hom.: 8

Bravo AF: 0.00283

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 23, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	3.9
Dann	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs377597654; hg19: chrX-40440272;