X-40588882-G-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.38-104G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00522 in 918,809 control chromosomes in the GnomAD database, including 11 homozygotes. There are 1,309 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (1 hom., 132 hem., cov: 23)
  • Exomes 𝑓: 0.0054 (10 hom. 1177 hem.)
• Consequence: ATP6AP2 NM_005765.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.795

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=-0.6).
• BP6: Variant X-40588882-G-A is Benign according to our data. Variant chrX-40588882-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 677623.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 132 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6AP2	NM_005765.3	c.38-104G>A		intron_variant		ENST00000636580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6AP2	ENST00000636580.2	c.38-104G>A		intron_variant		1	NM_005765.3	P3

Frequencies

GnomAD3 genomes AF: 0.00383 AC: 429 AN: 111989 Hom.: 1 Cov.: 23 AF XY: 0.00386 AC XY: 132 AN XY: 34159

Gnomad AFR AF: 0.000714

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00172

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000730

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00554

Gnomad OTH AF: 0.00199

GnomAD4 exome AF: 0.00542 AC: 4369 AN: 806766 Hom.: 10 AF XY: 0.00533 AC XY: 1177 AN XY: 221006

Gnomad4 AFR exome AF: 0.000693

Gnomad4 AMR exome AF: 0.00117

Gnomad4 ASJ exome AF: 0.000175

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000328

Gnomad4 FIN exome AF: 0.0172

Gnomad4 NFE exome AF: 0.00597

Gnomad4 OTH exome AF: 0.00458

GnomAD4 genome AF: 0.00383 AC: 429 AN: 112043 Hom.: 1 Cov.: 23 AF XY: 0.00386 AC XY: 132 AN XY: 34223

Gnomad4 AFR AF: 0.000713

Gnomad4 AMR AF: 0.00171

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000732

Gnomad4 FIN AF: 0.0148

Gnomad4 NFE AF: 0.00554

Gnomad4 OTH AF: 0.00197

Alfa AF: 0.00475 Hom.: 25

Bravo AF: 0.00300

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

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	-0.60
Cadd	Benign	5.8
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: rs140986900; hg19: chrX-40448134;