X-40597833-T-C

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.534+169T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.92 (33399 hom., 30521 hem., cov: 23)
  • Exomes 𝑓: 0.91 (111982 hom. 112418 hem.)
  • Failed GnomAD Quality Control
• Consequence: ATP6AP2 NM_005765.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0750

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=-1.0).
• BP6: Variant X-40597833-T-C is Benign according to our data. Variant chrX-40597833-T-C is described in ClinVar as [Benign]. Clinvar id is 1291912.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 33405 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6AP2	NM_005765.3	c.534+169T>C		intron_variant		ENST00000636580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6AP2	ENST00000636580.2	c.534+169T>C		intron_variant		1	NM_005765.3	P3

Frequencies

GnomAD3 genomes AF: 0.925 AC: 102492 AN: 110837 Hom.: 33405 Cov.: 23 AF XY: 0.923 AC XY: 30455 AN XY: 33007

Gnomad AFR AF: 0.974

Gnomad AMI AF: 0.869

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.932

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.970

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.932

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.914 AC: 358348 AN: 392042 Hom.: 111982 Cov.: 6 AF XY: 0.924 AC XY: 112418 AN XY: 121670

Gnomad4 AFR exome AF: 0.977

Gnomad4 AMR exome AF: 0.936

Gnomad4 ASJ exome AF: 0.942

Gnomad4 EAS exome AF: 0.871

Gnomad4 SAS exome AF: 0.963

Gnomad4 FIN exome AF: 0.893

Gnomad4 NFE exome AF: 0.908

Gnomad4 OTH exome AF: 0.919

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.925 AC: 102548 AN: 110891 Hom.: 33399 Cov.: 23 AF XY: 0.923 AC XY: 30521 AN XY: 33071

Gnomad4 AFR AF: 0.974

Gnomad4 AMR AF: 0.923

Gnomad4 ASJ AF: 0.932

Gnomad4 EAS AF: 0.836

Gnomad4 SAS AF: 0.959

Gnomad4 FIN AF: 0.875

Gnomad4 NFE AF: 0.907

Gnomad4 OTH AF: 0.930

Alfa AF: 0.914 Hom.: 8148

Bravo AF: 0.931

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.54
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: rs5918007; hg19: chrX-40457085;