rs724160012

Variant names:

• chrX-153548789-CTGGTCG-C
• rs724160012
• NM_001001344.3:c.1277_1282delTCGTGG

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PM4 PP3 PP5

The NM_001001344.3(ATP2B3):​c.1277_1282delTCGTGG​(p.Val426_Val427del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: ATP2B3 NM_001001344.3 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.90
• Publications: 2 publications found

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]

ATP2B3 Gene-Disease associations (from GenCC):

• X-linked progressive cerebellar ataxia

  Inheritance: XL, Unknown Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
• X-linked non progressive cerebellar ataxia

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001001344.3.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant X-153548789-CTGGTCG-C is Pathogenic according to our data. Variant chrX-153548789-CTGGTCG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 162470.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2B3	NM_001001344.3	c.1277_1282delTCGTGG	p.Val426_Val427del	disruptive_inframe_deletion	Exon 10 of 22	ENST00000263519.5	NP_001001344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2B3	ENST00000263519.5	c.1277_1282delTCGTGG	p.Val426_Val427del	disruptive_inframe_deletion	Exon 10 of 22	1	NM_001001344.3	ENSP00000263519.4

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Aldosterone-producing adrenal cortex adenoma Pathogenic:1

Feb 17, 2013

Institute of Human Genetics Munich, TUM University Hospital

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.9
Mutation Taster		=0/200	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs724160012; hg19: chrX-152814247;