X-154428787-T-TGGC

Variant names:

• chrX-154428787-T-TGGC
• rs781797236
• NM_001183.6:c.114_116dupGGC

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_001183.6(ATP6AP1):​c.114_116dupGGC​(p.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 0.000141 in 1,124,450 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 34 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., 5 hem., cov: 21)
  • Exomes 𝑓: 0.00012 (0 hom. 29 hem.)
• Consequence: ATP6AP1 NM_001183.6 disruptive_inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -12 ACMG points.

• BP6: Variant X-154428787-T-TGGC is Benign according to our data. Variant chrX-154428787-T-TGGC is described in ClinVar as [Likely_benign]. Clinvar id is 2058049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 5 XL,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6AP1	NM_001183.6	c.114_116dupGGC	p.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.114_116dupGGC	p.Ala39dup	disruptive_inframe_insertion	Exon 1 of 10	1	NM_001183.6	ENSP00000358777.2

Frequencies

GnomAD3 genomes AF: 0.000294 AC: 33 AN: 112150 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.000425

Gnomad AMI AF: 0.00880

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000644

Gnomad MID AF: 0.00426

Gnomad NFE AF: 0.000151

Gnomad OTH AF: 0.000660

GnomAD2 exomes AF: 0.000129 AC: 7 AN: 54469 AF XY: 0.0000686

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000183

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000674

Gnomad NFE exome AF: 0.0000938

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000124 AC: 126 AN: 1012259 Hom.: 0 Cov.: 31 AF XY: 0.0000890 AC XY: 29 AN XY: 325761

African (AFR) AF: 0.000826 AC: 17 AN: 20581

American (AMR) AF: 0.000132 AC: 3 AN: 22644

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

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

South Asian (SAS) AF: 0.000130 AC: 6 AN: 46150

European-Finnish (FIN) AF: 0.00112 AC: 32 AN: 28515

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3621

European-Non Finnish (NFE) AF: 0.0000719 AC: 58 AN: 806956

Other (OTH) AF: 0.000234 AC: 10 AN: 42724

GnomAD4 genome AF: 0.000294 AC: 33 AN: 112191 Hom.: 0 Cov.: 21 AF XY: 0.000145 AC XY: 5 AN XY: 34547

African (AFR) AF: 0.000424 AC: 13 AN: 30644

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: 0.000644 AC: 4 AN: 6209

Middle Eastern (MID) AF: 0.00467 AC: 1 AN: 214

European-Non Finnish (NFE) AF: 0.000151 AC: 8 AN: 53116

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

Alfa AF: 0.0000386 Hom.: 1

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inborn genetic diseases Benign:1

Nov 19, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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. -

not provided Benign:1

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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

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;