Variant ENST00000572116.1:c.399A>G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The ENST00000572116.1(ATP2A3):c.399A>G(p.Arg133Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,613,220 control chromosomes in the GnomAD database, including 104,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.32 ( 8348 hom., cov: 31)

Exomes 𝑓: 0.36 ( 95894 hom. )

Consequence

ATP2A3
ENST00000572116.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.46

Variant links:

Genes affected

ATP2A3 (HGNC:813): (ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3) This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in calcium sequestration associated with muscular excitation and contraction. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ATP2A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 17-3925408-T-C is Benign according to our data. Variant chr17-3925408-T-C is described in ClinVar as [Benign]. Clinvar id is 3059152.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2A3	NM_005173.4 link	c.*14A>G		3_prime_UTR_variant	Exon 21 of 21	ENST00000397041.8	NP_005164.2	Q93084-2A8K9K1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2A3	ENST00000397041 link	c.*14A>G		3_prime_UTR_variant	Exon 21 of 21	1	NM_005173.4	ENSP00000380234.3		Q93084-2

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48944

AN:

151776

Hom.:

8333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.498

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.299

Gnomad SAS

AF:

0.280

Gnomad FIN

AF:

0.319

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.369

Gnomad OTH

AF:

0.341

GnomAD3 exomes

AF:

0.352

AC:

87833

AN:

249482

Hom.:

16034

AF XY:

0.350

AC XY:

47234

AN XY:

134974

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.444

Gnomad ASJ exome

AF:

0.391

Gnomad EAS exome

AF:

0.282

Gnomad SAS exome

AF:

0.288

Gnomad FIN exome

AF:

0.323

Gnomad NFE exome

AF:

0.376

Gnomad OTH exome

AF:

0.357

GnomAD4 exome

AF:

0.360

AC:

526316

AN:

1461326

Hom.:

95894

Cov.:

AF XY:

0.358

AC XY:

260513

AN XY:

726950

show subpopulations

Gnomad4 AFR exome

AF:

0.204

Gnomad4 AMR exome

AF:

0.438

Gnomad4 ASJ exome

AF:

0.390

Gnomad4 EAS exome

AF:

0.301

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.327

Gnomad4 NFE exome

AF:

0.371

Gnomad4 OTH exome

AF:

0.349

GnomAD4 genome

AF:

0.323

AC:

49005

AN:

151894

Hom.:

8348

Cov.:

AF XY:

0.321

AC XY:

23842

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.403

Gnomad4 ASJ

AF:

0.402

Gnomad4 EAS

AF:

0.299

Gnomad4 SAS

AF:

0.281

Gnomad4 FIN

AF:

0.319

Gnomad4 NFE

AF:

0.369

Gnomad4 OTH

AF:

0.341

Alfa

AF:

0.364

Hom.:

15438

Bravo

AF:

0.329

Asia WGS

AF:

0.266

AC:

925

AN:

3478

EpiCase

AF:

0.368

EpiControl

AF:

0.372

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ATP2A3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 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

-0.58

CADD

Benign

DANN

Benign

0.48

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

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