rs2269414

chrX-153556438-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001001344.3(ATP2B3):c.2326+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 1,185,148 control chromosomes in the GnomAD database, including 4,718 homozygotes. There are 32,347 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.15 (1577 hom., 4487 hem., cov: 23)
  • Exomes 𝑓: 0.077 (3141 hom. 27860 hem.)
• Consequence: ATP2B3 NM_001001344.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

Genes affected

ATP2B3 (HGNC:816): (ATPase plasma membrane Ca2+ transporting 3) The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis. The mammalian plasma membrane calcium ATPase isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts. The expression of different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 3. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-153556438-C-T is Benign according to our data. Variant chrX-153556438-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP2B3	NM_001001344.3	c.2326+20C>T		intron_variant		ENST00000263519.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP2B3	ENST00000263519.5	c.2326+20C>T		intron_variant		1	NM_001001344.3	P1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 16382 AN: 110838 Hom.: 1575 Cov.: 23 AF XY: 0.135 AC XY: 4479 AN XY: 33106

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.0221

Gnomad AMR AF: 0.0660

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0653

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0511

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0683

Gnomad OTH AF: 0.145

GnomAD3 exomes AF: 0.0963 AC: 13763 AN: 142899 Hom.: 819 AF XY: 0.0959 AC XY: 4134 AN XY: 43113

Gnomad AFR exome AF: 0.359

Gnomad AMR exome AF: 0.0377

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.0849

Gnomad SAS exome AF: 0.135

Gnomad FIN exome AF: 0.0517

Gnomad NFE exome AF: 0.0680

Gnomad OTH exome AF: 0.0841

GnomAD4 exome AF: 0.0769 AC: 82619 AN: 1074258 Hom.: 3141 Cov.: 32 AF XY: 0.0802 AC XY: 27860 AN XY: 347176

Gnomad4 AFR exome AF: 0.360

Gnomad4 AMR exome AF: 0.0400

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.0671

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.0527

Gnomad4 NFE exome AF: 0.0635

Gnomad4 OTH exome AF: 0.0941

GnomAD4 genome AF: 0.148 AC: 16394 AN: 110890 Hom.: 1577 Cov.: 23 AF XY: 0.135 AC XY: 4487 AN XY: 33168

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.0658

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0655

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0511

Gnomad4 NFE AF: 0.0683

Gnomad4 OTH AF: 0.143

Alfa AF: 0.122 Hom.: 1200

Bravo AF: 0.157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.71
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2269414; hg19: chrX-152821896;