17-3929444-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005173.4(ATP2A3):c.2746G>A(p.Val916Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,590,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V916V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ATP2A3
NM_005173.4 missense, splice_region

Scores

Splicing: ADA: 0.0001329

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.510

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2289902).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005173.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP2A3	NM_005173.4	MANE Select	c.2746G>A	p.Val916Ile	missense splice_region	Exon 19 of 21	NP_005164.2
ATP2A3	NM_174953.3		c.2746G>A	p.Val916Ile	missense splice_region	Exon 19 of 23	NP_777613.1	Q93084-5
ATP2A3	NM_174954.3		c.2746G>A	p.Val916Ile	missense splice_region	Exon 19 of 23	NP_777614.1	Q93084-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP2A3	ENST00000397041.8	TSL:1 MANE Select	c.2746G>A	p.Val916Ile	missense splice_region	Exon 19 of 21	ENSP00000380234.3	Q93084-2
ATP2A3	ENST00000397043.7	TSL:1	c.2746G>A	p.Val916Ile	missense splice_region	Exon 19 of 21	ENSP00000380236.3	Q93084-4
ATP2A3	ENST00000570845.5	TSL:1	c.73G>A	p.Val25Ile	missense splice_region	Exon 2 of 6	ENSP00000461480.1	A0A0C4DGN3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000387

AC:

AN:

206752

AF XY:

0.0000358

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000127

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000224

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000174

AC:

AN:

1438572

Hom.:

Cov.:

AF XY:

0.0000196

AC XY:

AN XY:

713738

show subpopulations

African (AFR)

AF:

0.0000303

AC:

AN:

32958

American (AMR)

AF:

0.000120

AC:

AN:

41840

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25568

East Asian (EAS)

AF:

0.000104

AC:

AN:

38496

South Asian (SAS)

AF:

0.0000242

AC:

AN:

82790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50922

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4794

European-Non Finnish (NFE)

AF:

0.0000118

AC:

AN:

1101838

Other (OTH)

AF:

0.00

AC:

AN:

59366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41438

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

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:

0.0000387

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000333

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.43

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.70

M_CAP

Benign

0.066

MetaRNN

Benign

0.23

MetaSVM

Uncertain

0.20

MutationAssessor

Benign

0.72

PhyloP100

0.51

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.48

REVEL

Benign

0.27

Sift

Benign

0.047

Sift4G

Benign

0.083

Polyphen

0.0050

Vest4

0.24

MVP

0.44

MPC

0.44

ClinPred

0.078

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.035

gMVP

0.51

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.038

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