Variant 17-3930414-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005173.4(ATP2A3):c.2631C>A(p.Ser877Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 1,613,958 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 11 hom., cov: 31)

Exomes 𝑓: 0.00078 ( 13 hom. )

Consequence

ATP2A3
NM_005173.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.884

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:

ATP2A3 (HGNC:):

ATP2A3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 17-3930414-G-T is Benign according to our data. Variant chr17-3930414-G-T is described in ClinVar as [Benign]. Clinvar id is 781248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.884 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00718 (1094/152348) while in subpopulation AFR AF= 0.0249 (1037/41582). AF 95% confidence interval is 0.0237. There are 11 homozygotes in gnomad4. There are 505 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2A3	NM_005173.4 linkuse as main transcript	c.2631C>A	p.Ser877Ser	synonymous_variant	18/21	ENST00000397041.8	NP_005164.2	Q93084-2A8K9K1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2A3	ENST00000397041.8 linkuse as main transcript	c.2631C>A	p.Ser877Ser	synonymous_variant	18/21	1	NM_005173.4	ENSP00000380234.3		Q93084-2

Frequencies

GnomAD3 genomes

AF:

0.00710

AC:

1081

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

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:

0.0000294

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00184

AC:

460

AN:

249872

Hom.:

AF XY:

0.00142

AC XY:

193

AN XY:

135484

show subpopulations

Gnomad AFR exome

AF:

0.0253

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000777

AC:

1136

AN:

1461610

Hom.:

Cov.:

AF XY:

0.000655

AC XY:

476

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.0284

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.00718

AC:

1094

AN:

152348

Hom.:

Cov.:

AF XY:

0.00678

AC XY:

505

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0249

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.000408

Hom.:

Bravo

AF:

0.00825

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 11, 2017	- -

ATP2A3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 06, 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

-0.61

CADD

Benign

1.5

DANN

Benign

0.50

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