NM_001001344.3:c.122G>A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001001344.3(ATP2B3):c.122G>A(p.Arg41Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000882 in 113,422 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 1 hem., cov: 25)

Exomes 𝑓: 0.0000028 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

ATP2B3
NM_001001344.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

Publications

0 publications found

Variant links:

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

ATP2B3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.861

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP2B3	NM_001001344.3	MANE Select	c.122G>A	p.Arg41Gln	missense	Exon 3 of 22	NP_001001344.1	Q16720-1
ATP2B3	NM_001388362.1		c.122G>A	p.Arg41Gln	missense	Exon 3 of 22	NP_001375291.1
ATP2B3	NM_001388361.1		c.122G>A	p.Arg41Gln	missense	Exon 2 of 21	NP_001375290.1	Q16720-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP2B3	ENST00000263519.5	TSL:1 MANE Select	c.122G>A	p.Arg41Gln	missense	Exon 3 of 22	ENSP00000263519.4	Q16720-1
ATP2B3	ENST00000359149.9	TSL:1	c.122G>A	p.Arg41Gln	missense	Exon 3 of 23	ENSP00000352062.3	Q16720-2
ATP2B3	ENST00000496610.2	TSL:3	c.122G>A	p.Arg41Gln	missense	Exon 3 of 23	ENSP00000516173.1	A0A994J5M1

Frequencies

GnomAD3 genomes

AF:

0.00000882

AC:

AN:

113422

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000319

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000125

AC:

AN:

160596

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000288

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000275

AC:

AN:

1089543

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

357095

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26341

American (AMR)

AF:

0.00

AC:

AN:

34138

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19100

East Asian (EAS)

AF:

0.00

AC:

AN:

29914

South Asian (SAS)

AF:

0.00

AC:

AN:

52397

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39455

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3836

European-Non Finnish (NFE)

AF:

0.00000358

AC:

AN:

838646

Other (OTH)

AF:

0.00

AC:

AN:

45716

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000882

AC:

AN:

113422

Hom.:

Cov.:

AF XY:

0.0000281

AC XY:

AN XY:

35552

show subpopulations

African (AFR)

AF:

0.0000319

AC:

AN:

31310

American (AMR)

AF:

0.00

AC:

AN:

10838

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2661

East Asian (EAS)

AF:

0.00

AC:

AN:

3589

South Asian (SAS)

AF:

0.00

AC:

AN:

2827

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6333

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53400

Other (OTH)

AF:

0.00

AC:

AN:

1538

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.23

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.46

MetaRNN

Pathogenic

0.86

MetaSVM

Pathogenic

0.95

MutationAssessor

Pathogenic

3.4

PhyloP100

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.3

REVEL

Pathogenic

0.70

Sift

Benign

0.069

Sift4G

Uncertain

0.051

Polyphen

0.90

Vest4

0.66

MutPred

0.69

Gain of helix (P = 0.0696)

MVP

0.99

MPC

1.7

ClinPred

0.91

GERP RS

4.7

Varity_R

0.43

gMVP

0.74

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over