NM_001183.6:c.111_116dupGGCGGC

Variant names:

• chrX-154428787-T-TGGCGGC
• rs781797236
• NM_001183.6:c.111_116dupGGCGGC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001183.6(ATP6AP1):​c.111_116dupGGCGGC​(p.Ala38_Ala39dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,124,353 control chromosomes in the GnomAD database, including 1,267 homozygotes. There are 3,562 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (735 hom., 2048 hem., cov: 21)
  • Exomes 𝑓: 0.0066 (532 hom. 1514 hem.)
• Consequence: ATP6AP1 NM_001183.6 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• 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 Benign. Variant got -16 ACMG points.

• BP6: Variant X-154428787-T-TGGCGGC is Benign according to our data. Variant chrX-154428787-T-TGGCGGC is described in ClinVar as [Benign]. Clinvar id is 1165872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6AP1	NM_001183.6	c.111_116dupGGCGGC	p.Ala38_Ala39dup	disruptive_inframe_insertion	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.111_116dupGGCGGC	p.Ala38_Ala39dup	disruptive_inframe_insertion	Exon 1 of 10	1	NM_001183.6	ENSP00000358777.2

Frequencies

GnomAD3 genomes AF: 0.0710 AC: 7960 AN: 112046 Hom.: 735 Cov.: 21 AF XY: 0.0590 AC XY: 2030 AN XY: 34410

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0271

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000281

Gnomad SAS AF: 0.000709

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00851

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.0568

GnomAD3 exomes AF: 0.00470 AC: 256 AN: 54469 Hom.: 14 AF XY: 0.00220 AC XY: 32 AN XY: 14567

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.00733

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.000121

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000656

Gnomad OTH exome AF: 0.00421

GnomAD4 exome AF: 0.00662 AC: 6697 AN: 1012267 Hom.: 532 Cov.: 31 AF XY: 0.00465 AC XY: 1514 AN XY: 325735

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.000177

Gnomad4 EAS exome AF: 0.000249

Gnomad4 SAS exome AF: 0.000498

Gnomad4 FIN exome AF: 0.0000351

Gnomad4 NFE exome AF: 0.000595

Gnomad4 OTH exome AF: 0.0182

GnomAD4 genome AF: 0.0712 AC: 7978 AN: 112086 Hom.: 735 Cov.: 21 AF XY: 0.0594 AC XY: 2048 AN XY: 34460

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.0270

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000282

Gnomad4 SAS AF: 0.000356

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00107

Gnomad4 OTH AF: 0.0561

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

Nov 13, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

Nov 19, 2021

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

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;