chrX-154428787-TGGCGGCGGCGGC-T

Variant names:

• chrX-154428787-TGGCGGCGGCGGC-T
• rs781797236
• NM_001183.6:c.105_116delGGCGGCGGCGGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001183.6(ATP6AP1):​c.105_116delGGCGGCGGCGGC​(p.Ala36_Ala39del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ATP6AP1 NM_001183.6 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• Publications: 3 publications found

Genes affected

ATP6AP1 (HGNC:868): (ATPase H+ transporting accessory protein 1) This gene encodes a component of a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. Vacuolar ATPase (V-ATPase) is comprised of a cytosolic V1 (site of the ATP catalytic site) and a transmembrane V0 domain. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, and receptor-mediated endocytosis. The encoded protein of this gene may assist in the V-ATPase-mediated acidification of neuroendocrine secretory granules. This protein may also play a role in early development. [provided by RefSeq, Aug 2013]

ATP6AP1-DT (HGNC:25138): (ATP6AP1 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6AP1	NM_001183.6	c.105_116delGGCGGCGGCGGC	p.Ala36_Ala39del	disruptive_inframe_deletion	Exon 1 of 10	ENST00000369762.7	NP_001174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6AP1	ENST00000369762.7	c.105_116delGGCGGCGGCGGC	p.Ala36_Ala39del	disruptive_inframe_deletion	Exon 1 of 10	1	NM_001183.6	ENSP00000358777.2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1012550 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 325978

African (AFR) AF: 0.00 AC: 0 AN: 20805

American (AMR) AF: 0.00 AC: 0 AN: 22652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16951

East Asian (EAS) AF: 0.00 AC: 0 AN: 24117

South Asian (SAS) AF: 0.00 AC: 0 AN: 46153

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28515

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3622

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 806972

Other (OTH) AF: 0.00 AC: 0 AN: 42763

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.27

Splicing

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

Other links and lift over

dbSNP: rs781797236; hg19: chrX-153657133;