X-153536382-G-A
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_001001344.3(ATP2B3):c.135G>A(p.Ala45=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,204,198 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 45 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00066 ( 0 hom., 18 hem., cov: 25)
Exomes 𝑓: 0.000074 ( 0 hom. 27 hem. )
Consequence
ATP2B3
NM_001001344.3 synonymous
NM_001001344.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.59
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant X-153536382-G-A is Benign according to our data. Variant chrX-153536382-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041009.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-4.59 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000661 (75/113441) while in subpopulation AFR AF= 0.00188 (59/31346). AF 95% confidence interval is 0.0015. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd at 18 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP2B3 | NM_001001344.3 | c.135G>A | p.Ala45= | synonymous_variant | 3/22 | ENST00000263519.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP2B3 | ENST00000263519.5 | c.135G>A | p.Ala45= | synonymous_variant | 3/22 | 1 | NM_001001344.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000661 AC: 75AN: 113388Hom.: 0 Cov.: 25 AF XY: 0.000507 AC XY: 18AN XY: 35534
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GnomAD3 exomes AF: 0.000234 AC: 38AN: 162464Hom.: 0 AF XY: 0.000167 AC XY: 9AN XY: 53966
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GnomAD4 exome AF: 0.0000743 AC: 81AN: 1090757Hom.: 0 Cov.: 31 AF XY: 0.0000754 AC XY: 27AN XY: 358099
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ATP2B3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 25, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at