17-3935332-T-C

Position:

• chr17-3935332-T-C

Variant summary

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

The NM_005173.4(ATP2A3):​c.2525-55A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,512,930 control chromosomes in the GnomAD database, including 17,328 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 0.12 (1560 hom., cov: 31)
  • Exomes 𝑓: 0.13 (15768 hom.)
• Consequence: ATP2A3 NM_005173.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP2A3	NM_005173.4	c.2525-55A>G		intron_variant		ENST00000397041.8	NP_005164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP2A3	ENST00000397041.8	c.2525-55A>G		intron_variant		1	NM_005173.4	ENSP00000380234.3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18176 AN: 152098 Hom.: 1556 Cov.: 31

Gnomad AFR AF: 0.0671

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.130 AC: 176732 AN: 1360714 Hom.: 15768 AF XY: 0.131 AC XY: 89280 AN XY: 681728

Gnomad4 AFR exome AF: 0.0622

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.528

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.119 AC: 18182 AN: 152216 Hom.: 1560 Cov.: 31 AF XY: 0.125 AC XY: 9317 AN XY: 74400

Gnomad4 AFR AF: 0.0670

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0946 Hom.: 459

Bravo AF: 0.128

Asia WGS AF: 0.290 AC: 1007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2074991; hg19: chr17-3838626; COSMIC: COSV59228297; COSMIC: COSV59228297;