X-154428737-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001183.6(ATP6AP1):c.45G>A(p.Arg15=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,146,269 control chromosomes in the GnomAD database, including 5,214 homozygotes. There are 42,749 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (473 hom., 3776 hem., cov: 25)
  • Exomes 𝑓: 0.11 (4741 hom. 38973 hem.)
• Consequence: ATP6AP1 NM_001183.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.519

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant X-154428737-G-A is Benign according to our data. Variant chrX-154428737-G-A is described in ClinVar as [Benign]. Clinvar id is 770830.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.519 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6AP1	NM_001183.6	c.45G>A	p.Arg15=	synonymous_variant	1/10	ENST00000369762.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6AP1	ENST00000369762.7	c.45G>A	p.Arg15=	synonymous_variant	1/10	1	NM_001183.6	P1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 11909 AN: 113143 Hom.: 465 Cov.: 25 AF XY: 0.107 AC XY: 3768 AN XY: 35297

Gnomad AFR AF: 0.0915

Gnomad AMI AF: 0.00875

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0600

Gnomad EAS AF: 0.0617

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0464

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0930

GnomAD4 exome AF: 0.115 AC: 118410 AN: 1033077 Hom.: 4741 Cov.: 31 AF XY: 0.116 AC XY: 38973 AN XY: 335163

Gnomad4 AFR exome AF: 0.0854

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.0637

Gnomad4 EAS exome AF: 0.0744

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.112

GnomAD4 genome AF: 0.105 AC: 11928 AN: 113192 Hom.: 473 Cov.: 25 AF XY: 0.107 AC XY: 3776 AN XY: 35356

Gnomad4 AFR AF: 0.0914

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0600

Gnomad4 EAS AF: 0.0608

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.104

Alfa AF: 0.111 Hom.: 982

Bravo AF: 0.103

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	8.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28497482; hg19: chrX-153657083;