rs140986900

Variant names:

• chrX-40588882-G-A
• rs140986900
• NM_005765.3:c.38-104G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-40588882-G-A
• chrX-40588882-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_005765.3(ATP6AP2):​c.38-104G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00522 in 918,809 control chromosomes in the GnomAD database, including 11 homozygotes. There are 1,309 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 0.0038 (1 hom., 132 hem., cov: 23)
  • Exomes 𝑓: 0.0054 (10 hom. 1177 hem.)
• Consequence: ATP6AP2 NM_005765.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.795
• Publications: 0 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, AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• syndromic X-linked intellectual disability Hedera type

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

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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant X-40588882-G-A is Benign according to our data. Variant chrX-40588882-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 677623.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 132 XL,AR,Unknown gene

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.38-104G>A		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.38-104G>A		intron	N/A	ENSP00000490083.1	O75787-1
	ATP6AP2	ENST00000636639.1	TSL:1	n.38-104G>A		intron	N/A	ENSP00000490382.1	A0A1B0GV60
	ATP6AP2	ENST00000901377.1		c.38-104G>A		intron	N/A	ENSP00000571436.1

Frequencies

GnomAD3 genomes AF: 0.00383 AC: 429 AN: 111989 Hom.: 1 Cov.: 23

Gnomad AFR AF: 0.000714

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00172

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000730

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00554

Gnomad OTH AF: 0.00199

GnomAD4 exome AF: 0.00542 AC: 4369 AN: 806766 Hom.: 10 AF XY: 0.00533 AC XY: 1177 AN XY: 221006

African (AFR) AF: 0.000693 AC: 14 AN: 20198

American (AMR) AF: 0.00117 AC: 36 AN: 30667

Ashkenazi Jewish (ASJ) AF: 0.000175 AC: 3 AN: 17097

East Asian (EAS) AF: 0.00 AC: 0 AN: 27193

South Asian (SAS) AF: 0.000328 AC: 15 AN: 45710

European-Finnish (FIN) AF: 0.0172 AC: 573 AN: 33349

Middle Eastern (MID) AF: 0.00722 AC: 17 AN: 2356

European-Non Finnish (NFE) AF: 0.00597 AC: 3545 AN: 593976

Other (OTH) AF: 0.00458 AC: 166 AN: 36220

GnomAD4 genome AF: 0.00383 AC: 429 AN: 112043 Hom.: 1 Cov.: 23 AF XY: 0.00386 AC XY: 132 AN XY: 34223

African (AFR) AF: 0.000713 AC: 22 AN: 30869

American (AMR) AF: 0.00171 AC: 18 AN: 10503

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3614

South Asian (SAS) AF: 0.000732 AC: 2 AN: 2733

European-Finnish (FIN) AF: 0.0148 AC: 89 AN: 5995

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00554 AC: 295 AN: 53256

Other (OTH) AF: 0.00197 AC: 3 AN: 1524

Alfa AF: 0.00475 Hom.: 25

Bravo AF: 0.00300

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.8
DANN	Benign	0.59
PhyloP100		0.80
PromoterAI		-0.0016	Neutral
Mutation Taster		=99/1	polymorphism

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: rs140986900; hg19: chrX-40448134;