X-153536395-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001001344.3(ATP2B3):c.148G>A(p.Glu50Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,204,825 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000015 ( 0 hom. 4 hem. )

Consequence

ATP2B3
NM_001001344.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.756

Publications

1 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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052879125).

BS2

High Hemizygotes in GnomAdExome4 at 4 XL,Unknown gene

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.148G>A	p.Glu50Lys	missense	Exon 3 of 22	NP_001001344.1	Q16720-1
ATP2B3	NM_001388362.1		c.148G>A	p.Glu50Lys	missense	Exon 3 of 22	NP_001375291.1
ATP2B3	NM_001388361.1		c.148G>A	p.Glu50Lys	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.148G>A	p.Glu50Lys	missense	Exon 3 of 22	ENSP00000263519.4	Q16720-1
ATP2B3	ENST00000359149.9	TSL:1	c.148G>A	p.Glu50Lys	missense	Exon 3 of 23	ENSP00000352062.3	Q16720-2
ATP2B3	ENST00000496610.2	TSL:3	c.148G>A	p.Glu50Lys	missense	Exon 3 of 23	ENSP00000516173.1	A0A994J5M1

Frequencies

GnomAD3 genomes

AF:

0.00000882

AC:

AN:

113367

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000320

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:

0.0000122

AC:

AN:

164025

AF XY:

0.0000182

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:

0.0000140

Gnomad OTH exome

AF:

0.000242

GnomAD4 exome

AF:

0.0000147

AC:

AN:

1091458

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

358616

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26353

American (AMR)

AF:

0.00

AC:

AN:

34441

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19149

East Asian (EAS)

AF:

0.00

AC:

AN:

30013

South Asian (SAS)

AF:

0.00

AC:

AN:

52622

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39734

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3632

European-Non Finnish (NFE)

AF:

0.0000167

AC:

AN:

839738

Other (OTH)

AF:

0.0000437

AC:

AN:

45776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

113367

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35491

show subpopulations

African (AFR)

AF:

0.0000320

AC:

AN:

31280

American (AMR)

AF:

0.00

AC:

AN:

10828

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2664

East Asian (EAS)

AF:

0.00

AC:

AN:

3589

South Asian (SAS)

AF:

0.00

AC:

AN:

2818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53386

Other (OTH)

AF:

0.00

AC:

AN:

1539

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000113

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

Benign

0.075

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.047

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.72

M_CAP

Benign

0.053

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.59

MutationAssessor

Benign

-0.75

PhyloP100

0.76

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.42

REVEL

Uncertain

0.34

Sift

Benign

0.96

Sift4G

Benign

0.90

Polyphen

0.0

Vest4

0.11

MVP

0.84

MPC

0.64

ClinPred

0.022

GERP RS

4.0

Varity_R

0.16

gMVP

0.69

Mutation Taster

=100/0

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over