rs5918007

Variant names:

• chrX-40597833-T-C
• rs5918007
• NM_005765.3:c.534+169T>C

Your query was ambiguous. Multiple possible variants found:

• chrX-40597833-T-C
• chrX-40597833-T-A
• chrX-40597833-T-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

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
• Publications: 5 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: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• syndromic X-linked intellectual disability Hedera type

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

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

ACMG classification

Our verdict: Likely_benign. The variant received -6 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 VariationId is 1291912.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005765.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6AP2	NM_005765.3	MANE Select	c.534+169T>C		intron	N/A	NP_005756.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6AP2	ENST00000636580.2	TSL:1 MANE Select	c.534+169T>C		intron	N/A	ENSP00000490083.1	O75787-1
	ATP6AP2	ENST00000636639.1	TSL:1	n.534+169T>C		intron	N/A	ENSP00000490382.1	A0A1B0GV60
	ATP6AP2	ENST00000901377.1		c.534+169T>C		intron	N/A	ENSP00000571436.1

Frequencies

GnomAD3 genomes AF: 0.925 AC: 102492 AN: 110837 Hom.: 33405 Cov.: 23

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

African (AFR) AF: 0.977 AC: 10813 AN: 11066

American (AMR) AF: 0.936 AC: 16914 AN: 18074

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 10674 AN: 11334

East Asian (EAS) AF: 0.871 AC: 19822 AN: 22748

South Asian (SAS) AF: 0.963 AC: 29291 AN: 30411

European-Finnish (FIN) AF: 0.893 AC: 20938 AN: 23448

Middle Eastern (MID) AF: 0.969 AC: 1547 AN: 1596

European-Non Finnish (NFE) AF: 0.908 AC: 228336 AN: 251584

Other (OTH) AF: 0.919 AC: 20013 AN: 21781

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

African (AFR) AF: 0.974 AC: 29757 AN: 30553

American (AMR) AF: 0.923 AC: 9550 AN: 10350

Ashkenazi Jewish (ASJ) AF: 0.932 AC: 2466 AN: 2646

East Asian (EAS) AF: 0.836 AC: 2969 AN: 3550

South Asian (SAS) AF: 0.959 AC: 2497 AN: 2603

European-Finnish (FIN) AF: 0.875 AC: 5115 AN: 5844

Middle Eastern (MID) AF: 0.967 AC: 206 AN: 213

European-Non Finnish (NFE) AF: 0.907 AC: 47992 AN: 52942

Other (OTH) AF: 0.930 AC: 1410 AN: 1516

Alfa AF: 0.925 Hom.: 18705

Bravo AF: 0.931

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.54
DANN	Benign	0.59
PhyloP100		0.075
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: rs5918007; hg19: chrX-40457085;