rs181188218

Variant names:

• chrX-40580783-G-T
• rs181188218
• ENST00000436783.6:c.-111+1036G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000436783.6(ATP6AP2):​c.-111+1036G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00383 in 411,542 control chromosomes in the GnomAD database, including 18 homozygotes. There are 388 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 0.0098 (13 hom., 289 hem., cov: 25)
  • Exomes 𝑓: 0.0016 (5 hom. 99 hem.)
• Consequence: ATP6AP2 ENST00000436783.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.53

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant X-40580783-G-T is Benign according to our data. Variant chrX-40580783-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 674230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00981 (1107/112827) while in subpopulation AFR AF= 0.0339 (1053/31068). AF 95% confidence interval is 0.0322. There are 13 homozygotes in gnomad4. There are 289 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6AP2	NM_005765.3	c.-283G>T		upstream_gene_variant		ENST00000636580.2	NP_005756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6AP2	ENST00000636580.2	c.-283G>T		upstream_gene_variant		1	NM_005765.3	ENSP00000490083.1

Frequencies

GnomAD3 genomes AF: 0.00982 AC: 1108 AN: 112774 Hom.: 13 Cov.: 25 AF XY: 0.00828 AC XY: 289 AN XY: 34920

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00316

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000359

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000113

Gnomad OTH AF: 0.00860

GnomAD4 exome AF: 0.00157 AC: 470 AN: 298715 Hom.: 5 AF XY: 0.00105 AC XY: 99 AN XY: 94031

Gnomad4 AFR exome AF: 0.0349

Gnomad4 AMR exome AF: 0.00306

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000464

Gnomad4 OTH exome AF: 0.00321

GnomAD4 genome AF: 0.00981 AC: 1107 AN: 112827 Hom.: 13 Cov.: 25 AF XY: 0.00826 AC XY: 289 AN XY: 34983

Gnomad4 AFR AF: 0.0339

Gnomad4 AMR AF: 0.00315

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000360

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000113

Gnomad4 OTH AF: 0.00849

Alfa AF: 0.00819 Hom.: 24

Bravo AF: 0.0120

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.74
CADD	Benign	12
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs181188218; hg19: chrX-40440035;