rs8064630

Positions:

• chr17-3939197-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000397041.8(ATP2A3):​c.2101-1561C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 151,958 control chromosomes in the GnomAD database, including 2,567 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2567 hom., cov: 31)
• Consequence: ATP2A3 ENST00000397041.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2A3	NM_005173.4	c.2101-1561C>T		intron_variant		ENST00000397041.8	NP_005164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2A3	ENST00000397041.8	c.2101-1561C>T		intron_variant		1	NM_005173.4	ENSP00000380234	P1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27410 AN: 151840 Hom.: 2568 Cov.: 31

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.0615

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.180

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.180 AC: 27427 AN: 151958 Hom.: 2567 Cov.: 31 AF XY: 0.177 AC XY: 13130 AN XY: 74284

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.0609

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.178

Alfa AF: 0.187 Hom.: 626

Bravo AF: 0.187

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.49

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

Other links and lift over

dbSNP: rs8064630; hg19: chr17-3842491;