X-154428498-T-G

Variant names:

• chrX-154428498-T-G
• rs189401774
• ENST00000360656.5:n.52A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The ENST00000360656.5(ATP6AP1-DT):​n.52A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 520,654 control chromosomes in the GnomAD database, including 298 homozygotes. There are 1,627 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (239 hom., 1233 hem., cov: 25)
  • Exomes 𝑓: 0.0042 (59 hom. 394 hem.)
• Consequence: ATP6AP1-DT ENST00000360656.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0810
• Publications: 1 publications found

Genes affected

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

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 Gene-Disease associations (from GenCC):

• immunodeficiency 47

  Inheritance: XL, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Illumina, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital disorder of glycosylation type II

  Inheritance: XL Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant X-154428498-T-G is Benign according to our data. Variant chrX-154428498-T-G is described in ClinVar as [Benign]. Clinvar id is 1229930.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6AP1	NM_001183.6	c.-195T>G		upstream_gene_variant		ENST00000369762.7	NP_001174.2
ATP6AP1-DT	NR_103768.1	n.-19A>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6AP1	ENST00000369762.7	c.-195T>G		upstream_gene_variant		1	NM_001183.6	ENSP00000358777.2

Frequencies

GnomAD3 genomes AF: 0.0399 AC: 4503 AN: 112842 Hom.: 237 Cov.: 25

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0163

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000718

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.000694

Gnomad OTH AF: 0.0314

GnomAD4 exome AF: 0.00417 AC: 1700 AN: 407759 Hom.: 59 Cov.: 6 AF XY: 0.00342 AC XY: 394 AN XY: 115069

African (AFR) AF: 0.144 AC: 1193 AN: 8312

American (AMR) AF: 0.0100 AC: 81 AN: 8087

Ashkenazi Jewish (ASJ) AF: 0.000108 AC: 1 AN: 9228

East Asian (EAS) AF: 0.00 AC: 0 AN: 18591

South Asian (SAS) AF: 0.000246 AC: 6 AN: 24419

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22073

Middle Eastern (MID) AF: 0.00554 AC: 8 AN: 1445

European-Non Finnish (NFE) AF: 0.000503 AC: 148 AN: 294012

Other (OTH) AF: 0.0122 AC: 263 AN: 21592

GnomAD4 genome AF: 0.0400 AC: 4516 AN: 112895 Hom.: 239 Cov.: 25 AF XY: 0.0352 AC XY: 1233 AN XY: 35075

African (AFR) AF: 0.137 AC: 4253 AN: 31042

American (AMR) AF: 0.0163 AC: 176 AN: 10798

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2657

East Asian (EAS) AF: 0.00 AC: 0 AN: 3596

South Asian (SAS) AF: 0.000360 AC: 1 AN: 2779

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6281

Middle Eastern (MID) AF: 0.00459 AC: 1 AN: 218

European-Non Finnish (NFE) AF: 0.000694 AC: 37 AN: 53294

Other (OTH) AF: 0.0310 AC: 48 AN: 1546

Alfa AF: 0.00754 Hom.: 26

Bravo AF: 0.0464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 24, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.3
DANN	Benign	0.36
PhyloP100		0.081
PromoterAI		-0.042	Neutral

Splicing

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

Other links and lift over

dbSNP: rs189401774; hg19: chrX-153656844;