rs1060063

Variant names:

• chrX-40606564-T-C
• rs1060063
• ENST00000636639.1:n.*1315T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000636639.1(ATP6AP2):​n.*1315T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 111,842 control chromosomes in the GnomAD database, including 2,279 homozygotes. There are 4,610 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (2279 hom., 4610 hem., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ATP6AP2 ENST00000636639.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14
• Publications: 2 publications found

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]

ATP6AP2 Gene-Disease associations (from GenCC):

• ATP6AP2-related disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• congenital disorder of glycosylation, type IIr

  Inheritance: AR, XL Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• syndromic X-linked intellectual disability Hedera type

  Inheritance: XL Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• X-linked parkinsonism-spasticity syndrome

  Inheritance: XL, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000636639.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6AP2	NM_005765.3	MANE Select	c.*809T>C		3_prime_UTR	Exon 9 of 9	NP_005756.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6AP2	ENST00000636639.1	TSL:1	n.*1315T>C		non_coding_transcript_exon	Exon 10 of 10	ENSP00000490382.1
	ATP6AP2	ENST00000636580.2	TSL:1 MANE Select	c.*809T>C		3_prime_UTR	Exon 9 of 9	ENSP00000490083.1
	ATP6AP2	ENST00000636639.1	TSL:1	n.*1315T>C		3_prime_UTR	Exon 10 of 10	ENSP00000490382.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 16158 AN: 111789 Hom.: 2279 Cov.: 23

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0175

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.0502

Gnomad NFE AF: 0.00586

Gnomad OTH AF: 0.140

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 302 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 130

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 298

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1

Other (OTH) AF: 0.00 AC: 0 AN: 3

GnomAD4 genome AF: 0.145 AC: 16180 AN: 111842 Hom.: 2279 Cov.: 23 AF XY: 0.135 AC XY: 4610 AN XY: 34062

African (AFR) AF: 0.421 AC: 12887 AN: 30595

American (AMR) AF: 0.198 AC: 2074 AN: 10499

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 46 AN: 2653

East Asian (EAS) AF: 0.159 AC: 569 AN: 3568

South Asian (SAS) AF: 0.0168 AC: 46 AN: 2735

European-Finnish (FIN) AF: 0.00424 AC: 26 AN: 6135

Middle Eastern (MID) AF: 0.0459 AC: 10 AN: 218

European-Non Finnish (NFE) AF: 0.00586 AC: 312 AN: 53227

Other (OTH) AF: 0.138 AC: 210 AN: 1525

Alfa AF: 0.0941 Hom.: 1056

Bravo AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.6
DANN	Benign	0.81
PhyloP100		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1060063; hg19: chrX-40465816;