Variant X-153541366-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001001344.3(ATP2B3):c.216G>A(p.Ala72=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,210,503 control chromosomes in the GnomAD database, including 19 homozygotes. There are 844 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 3 hom., 146 hem., cov: 24)

Exomes 𝑓: 0.0018 ( 16 hom. 698 hem. )

Consequence

ATP2B3
NM_001001344.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -6.05

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant X-153541366-G-A is Benign according to our data. Variant chrX-153541366-G-A is described in ClinVar as [Benign]. Clinvar id is 787196.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-6.05 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00238 (268/112513) while in subpopulation NFE AF= 0.00139 (74/53211). AF 95% confidence interval is 0.00114. There are 3 homozygotes in gnomad4. There are 146 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2B3	NM_001001344.3 linkuse as main transcript	c.216G>A	p.Ala72=	synonymous_variant	4/22	ENST00000263519.5	NP_001001344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2B3	ENST00000263519.5 linkuse as main transcript	c.216G>A	p.Ala72=	synonymous_variant	4/22	1	NM_001001344.3	ENSP00000263519	P1	Q16720-1

Frequencies

GnomAD3 genomes

AF:

0.00238

AC:

268

AN:

112462

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

146

AN XY:

34616

show subpopulations

Gnomad AFR

AF:

0.0000323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000363

Gnomad FIN

AF:

0.0308

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.00139

Gnomad OTH

AF:

0.000661

GnomAD3 exomes

AF:

0.00328

AC:

601

AN:

183030

Hom.:

AF XY:

0.00319

AC XY:

216

AN XY:

67652

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS exome

AF:

0.00226

Gnomad FIN exome

AF:

0.0271

Gnomad NFE exome

AF:

0.00137

Gnomad OTH exome

AF:

0.00221

GnomAD4 exome

AF:

0.00185

AC:

2026

AN:

1097990

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

698

AN XY:

363476

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.00266

Gnomad4 FIN exome

AF:

0.0257

Gnomad4 NFE exome

AF:

0.000905

Gnomad4 OTH exome

AF:

0.00156

GnomAD4 genome

AF:

0.00238

AC:

268

AN:

112513

Hom.:

Cov.:

AF XY:

0.00421

AC XY:

146

AN XY:

34677

show subpopulations

Gnomad4 AFR

AF:

0.0000322

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000364

Gnomad4 FIN

AF:

0.0308

Gnomad4 NFE

AF:

0.00139

Gnomad4 OTH

AF:

0.000653

Alfa

AF:

0.00254

Hom.:

Bravo

AF:

0.000510

EpiCase

AF:

0.000654

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 14, 2018

- -

ATP2B3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.049

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over