X-154428787-T-TGGCGGCGGC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001183.6(ATP6AP1):c.108_116dup(p.Ala39_Ala41dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,124,742 control chromosomes in the GnomAD database, including 1 homozygotes. There are 35 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., 13 hem., cov: 21)
  • Exomes 𝑓: 0.000095 (1 hom. 22 hem.)
• Consequence: ATP6AP1 NM_001183.6 inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.146

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant X-154428787-T-TGGCGGCGGC is Benign according to our data. Variant chrX-154428787-T-TGGCGGCGGC is described in ClinVar as [Likely_benign]. Clinvar id is 1596406.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6AP1	NM_001183.6	c.108_116dup	p.Ala39_Ala41dup	inframe_insertion	1/10	ENST00000369762.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6AP1	ENST00000369762.7	c.108_116dup	p.Ala39_Ala41dup	inframe_insertion	1/10	1	NM_001183.6	P1

Frequencies

GnomAD3 genomes AF: 0.000651 AC: 73 AN: 112151 Hom.: 0 Cov.: 21 AF XY: 0.000348 AC XY: 12 AN XY: 34497

Gnomad AFR AF: 0.00232

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.000660

GnomAD3 exomes AF: 0.0000734 AC: 4 AN: 54469 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14567

Gnomad AFR exome AF: 0.00245

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000602

GnomAD4 exome AF: 0.0000948 AC: 96 AN: 1012550 Hom.: 1 Cov.: 31 AF XY: 0.0000675 AC XY: 22 AN XY: 325976

Gnomad4 AFR exome AF: 0.00274

Gnomad4 AMR exome AF: 0.0000441

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000217

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000136

Gnomad4 OTH exome AF: 0.000514

GnomAD4 genome AF: 0.000660 AC: 74 AN: 112192 Hom.: 0 Cov.: 21 AF XY: 0.000376 AC XY: 13 AN XY: 34548

Gnomad4 AFR AF: 0.00235

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.000652

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 25, 2023

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs781797236; hg19: chrX-153657133;