X-40588704-T-TTTTG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005765.3(ATP6AP2):c.38-274_38-271dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.93 (33922 hom., 27622 hem., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: ATP6AP2 NM_005765.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.631

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant X-40588704-T-TTTTG is Benign according to our data. Variant chrX-40588704-T-TTTTG is described in ClinVar as [Benign]. Clinvar id is 668777.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 33928 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6AP2	NM_005765.3	c.38-274_38-271dup		intron_variant		ENST00000636580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6AP2	ENST00000636580.2	c.38-274_38-271dup		intron_variant		1	NM_005765.3	P3

Frequencies

GnomAD3 genomes AF: 0.932 AC: 100032 AN: 107320 Hom.: 33928 Cov.: 0 AF XY: 0.927 AC XY: 27555 AN XY: 29728

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.932

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.966

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.940

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.932 AC: 100088 AN: 107373 Hom.: 33922 Cov.: 0 AF XY: 0.927 AC XY: 27622 AN XY: 29793

Gnomad4 AFR AF: 0.986

Gnomad4 AMR AF: 0.930

Gnomad4 ASJ AF: 0.932

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.957

Gnomad4 FIN AF: 0.872

Gnomad4 NFE AF: 0.913

Gnomad4 OTH AF: 0.938

Alfa AF: 0.911 Hom.: 7083

Asia WGS AF: 0.904 AC: 2278 AN: 2519

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

Nov 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs72178914; hg19: chrX-40447956;