X-154428787-T-TGGCGGCGGC

Variant names:

• chrX-154428787-T-TGGCGGCGGC
• rs781797236
• NM_001183.6:c.108_116dupGGCGGCGGC

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001183.6(ATP6AP1):​c.108_116dupGGCGGCGGC​(p.Ala37_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 0.000151 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 disruptive_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.146
• 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: Likely_benign. The variant received -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 GnomAd4 at 13 XL,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6AP1	NM_001183.6	c.108_116dupGGCGGCGGC	p.Ala37_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.108_116dupGGCGGCGGC	p.Ala37_Ala39dup	disruptive_inframe_insertion	Exon 1 of 10	1	NM_001183.6	ENSP00000358777.2

Frequencies

GnomAD3 genomes AF: 0.000651 AC: 73 AN: 112151 Hom.: 0 Cov.: 21

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

GnomAD2 exomes AF: 0.0000734 AC: 4 AN: 54469 AF XY: 0.00

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 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

African (AFR) AF: 0.00274 AC: 57 AN: 20801

American (AMR) AF: 0.0000441 AC: 1 AN: 22655

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

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

South Asian (SAS) AF: 0.0000217 AC: 1 AN: 46153

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

Middle Eastern (MID) AF: 0.00110 AC: 4 AN: 3624

European-Non Finnish (NFE) AF: 0.0000136 AC: 11 AN: 806971

Other (OTH) AF: 0.000514 AC: 22 AN: 42763

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

African (AFR) AF: 0.00235 AC: 72 AN: 30645

American (AMR) AF: 0.00 AC: 0 AN: 10797

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2641

East Asian (EAS) AF: 0.00 AC: 0 AN: 3543

South Asian (SAS) AF: 0.00 AC: 0 AN: 2811

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6209

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 214

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53116

Other (OTH) AF: 0.000652 AC: 1 AN: 1534

Alfa AF: 0.00 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15
Mutation Taster		=86/14	polymorphism

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;