17-3935332-T-C

Variant names:

• chr17-3935332-T-C
• rs2074991
• NM_005173.4:c.2525-55A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.91).
• 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 rank	MANE	Protein	UniProt
ATP2A3	NM_005173.4	c.2525-55A>G		intron_variant	Intron 16 of 20	ENST00000397041.8	NP_005164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2A3	ENST00000397041.8	c.2525-55A>G		intron_variant	Intron 16 of 20	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

African (AFR) AF: 0.0622 AC: 1956 AN: 31450

American (AMR) AF: 0.244 AC: 10807 AN: 44318

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3627 AN: 25500

East Asian (EAS) AF: 0.528 AC: 20646 AN: 39138

South Asian (SAS) AF: 0.186 AC: 15649 AN: 84280

European-Finnish (FIN) AF: 0.115 AC: 5386 AN: 46710

Middle Eastern (MID) AF: 0.118 AC: 645 AN: 5472

European-Non Finnish (NFE) AF: 0.107 AC: 110364 AN: 1026754

Other (OTH) AF: 0.134 AC: 7652 AN: 57092

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

African (AFR) AF: 0.0670 AC: 2783 AN: 41548

American (AMR) AF: 0.179 AC: 2730 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 516 AN: 3470

East Asian (EAS) AF: 0.496 AC: 2556 AN: 5156

South Asian (SAS) AF: 0.201 AC: 967 AN: 4816

European-Finnish (FIN) AF: 0.114 AC: 1208 AN: 10604

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7045 AN: 68020

Other (OTH) AF: 0.109 AC: 231 AN: 2114

Alfa AF: 0.106 Hom.: 1342

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
PhyloP100		-0.0020
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2074991; hg19: chr17-3838626; COSMIC: COSV59228297; COSMIC: COSV59228297;