NM_001001344.3:c.209-17T>A

Variant names:

• chrX-153541342-T-A
• NM_001001344.3:c.209-17T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001001344.3(ATP2B3):​c.209-17T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,696 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: ATP2B3 NM_001001344.3 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.783
• Publications: 0 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: Unknown, XL Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• X-linked non progressive cerebellar ataxia

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001344.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B3	NM_001001344.3	MANE Select	c.209-17T>A		intron	N/A	NP_001001344.1	Q16720-1
	ATP2B3	NM_001388362.1		c.209-17T>A		intron	N/A	NP_001375291.1
	ATP2B3	NM_001388361.1		c.209-17T>A		intron	N/A	NP_001375290.1	Q16720-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2B3	ENST00000263519.5	TSL:1 MANE Select	c.209-17T>A		intron	N/A	ENSP00000263519.4	Q16720-1
	ATP2B3	ENST00000359149.9	TSL:1	c.209-17T>A		intron	N/A	ENSP00000352062.3	Q16720-2
	ATP2B3	ENST00000496610.2	TSL:3	c.209-17T>A		intron	N/A	ENSP00000516173.1	A0A994J5M1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097696 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363234

African (AFR) AF: 0.00 AC: 0 AN: 26394

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

East Asian (EAS) AF: 0.00 AC: 0 AN: 30204

South Asian (SAS) AF: 0.00 AC: 0 AN: 54126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841942

Other (OTH) AF: 0.00 AC: 0 AN: 46080

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	See cases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.74
PhyloP100		-0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chrX-152806800;