X-40580818-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000436783.6(ATP6AP2):c.-111+1071A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 455,715 control chromosomes in the GnomAD database, including 7 homozygotes. There are 283 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 0.0066 (7 hom., 208 hem., cov: 24)
  • Exomes 𝑓: 0.0010 (0 hom. 75 hem.)
• Consequence: ATP6AP2 ENST00000436783.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.17

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant X-40580818-A-T is Benign according to our data. Variant chrX-40580818-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 677651.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00665 (746/112210) while in subpopulation AFR AF= 0.0228 (705/30914). AF 95% confidence interval is 0.0214. There are 7 homozygotes in gnomad4. There are 208 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6AP2	ENST00000436783.6	c.-111+1071A>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00665 AC: 746 AN: 112156 Hom.: 7 Cov.: 24 AF XY: 0.00604 AC XY: 208 AN XY: 34424

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00270

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000363

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000943

Gnomad OTH AF: 0.00398

GnomAD4 exome AF: 0.00101 AC: 348 AN: 343505 Hom.: 0 AF XY: 0.000661 AC XY: 75 AN XY: 113491

Gnomad4 AFR exome AF: 0.0219

Gnomad4 AMR exome AF: 0.00241

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: 0.0000150

Gnomad4 OTH exome AF: 0.00251

GnomAD4 genome AF: 0.00665 AC: 746 AN: 112210 Hom.: 7 Cov.: 24 AF XY: 0.00603 AC XY: 208 AN XY: 34488

Gnomad4 AFR AF: 0.0228

Gnomad4 AMR AF: 0.00270

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000364

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000943

Gnomad4 OTH AF: 0.00393

Alfa AF: 0.00512 Hom.: 15

Bravo AF: 0.00789

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 19, 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	-0.77
Cadd	Benign	1.2
Dann	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs191737410; hg19: chrX-40440070;