rs8064630

Variant names:

• chr17-3939197-G-A
• rs8064630
• NM_005173.4:c.2101-1561C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005173.4(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 NM_005173.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ATP2A3	NM_005173.4	c.2101-1561C>T		intron_variant	Intron 14 of 20	ENST00000397041.8	NP_005164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2A3	ENST00000397041.8	c.2101-1561C>T		intron_variant	Intron 14 of 20	1	NM_005173.4	ENSP00000380234.3

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

African (AFR) AF: 0.195 AC: 8104 AN: 41460

American (AMR) AF: 0.183 AC: 2787 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 976 AN: 3458

East Asian (EAS) AF: 0.0609 AC: 315 AN: 5174

South Asian (SAS) AF: 0.176 AC: 848 AN: 4810

European-Finnish (FIN) AF: 0.118 AC: 1252 AN: 10570

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12558 AN: 67916

Other (OTH) AF: 0.178 AC: 376 AN: 2110

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
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8064630; hg19: chr17-3842491;