NM_005765.3:c.38-274_38-271dupGTTT

Variant names:

• chrX-40588704-T-TTTTG
• rs72178914
• NM_005765.3:c.38-274_38-271dupGTTT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_005765.3(ATP6AP2):​c.38-274_38-271dupGTTT 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
• 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 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 -2 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 VariationId is 668777.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.38-274_38-271dupGTTT		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.38-282_38-281insTTTG		intron	N/A	ENSP00000490083.1	O75787-1
	ATP6AP2	ENST00000636639.1	TSL:1	n.38-282_38-281insTTTG		intron	N/A	ENSP00000490382.1	A0A1B0GV60
	ATP6AP2	ENST00000901377.1		c.38-282_38-281insTTTG		intron	N/A	ENSP00000571436.1

Frequencies

GnomAD3 genomes AF: 0.932 AC: 100032 AN: 107320 Hom.: 33928 Cov.: 0

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

African (AFR) AF: 0.986 AC: 29079 AN: 29499

American (AMR) AF: 0.930 AC: 9142 AN: 9830

Ashkenazi Jewish (ASJ) AF: 0.932 AC: 2410 AN: 2586

East Asian (EAS) AF: 0.831 AC: 2793 AN: 3361

South Asian (SAS) AF: 0.957 AC: 2305 AN: 2408

European-Finnish (FIN) AF: 0.872 AC: 4582 AN: 5255

Middle Eastern (MID) AF: 0.962 AC: 205 AN: 213

European-Non Finnish (NFE) AF: 0.913 AC: 47573 AN: 52099

Other (OTH) AF: 0.938 AC: 1361 AN: 1451

Alfa AF: 0.911 Hom.: 7083

Asia WGS AF: 0.904 AC: 2278 AN: 2519

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
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs72178914; hg19: chrX-40447956;