17-3925408-T-C

Variant names:

• chr17-3925408-T-C
• rs887387
• ENST00000572116.1:c.399A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The ENST00000572116.1(ATP2A3):​c.399A>G​(p.Arg133Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,613,220 control chromosomes in the GnomAD database, including 104,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.32 (8348 hom., cov: 31)
  • Exomes 𝑓: 0.36 (95894 hom.)
• Consequence: ATP2A3 ENST00000572116.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.46
• Publications: 24 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 17-3925408-T-C is Benign according to our data. Variant chr17-3925408-T-C is described in ClinVar as Benign. ClinVar VariationId is 3059152.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.46 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2A3	NM_005173.4	c.*14A>G		3_prime_UTR_variant	Exon 21 of 21	ENST00000397041.8	NP_005164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2A3	ENST00000397041.8	c.*14A>G		3_prime_UTR_variant	Exon 21 of 21	1	NM_005173.4	ENSP00000380234.3

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48944 AN: 151776 Hom.: 8333 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.341

GnomAD2 exomes AF: 0.352 AC: 87833 AN: 249482 AF XY: 0.350

Gnomad AFR exome AF: 0.203

Gnomad AMR exome AF: 0.444

Gnomad ASJ exome AF: 0.391

Gnomad EAS exome AF: 0.282

Gnomad FIN exome AF: 0.323

Gnomad NFE exome AF: 0.376

Gnomad OTH exome AF: 0.357

GnomAD4 exome AF: 0.360 AC: 526316 AN: 1461326 Hom.: 95894 Cov.: 50 AF XY: 0.358 AC XY: 260513 AN XY: 726950

African (AFR) AF: 0.204 AC: 6819 AN: 33480

American (AMR) AF: 0.438 AC: 19554 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 10182 AN: 26124

East Asian (EAS) AF: 0.301 AC: 11946 AN: 39694

South Asian (SAS) AF: 0.290 AC: 25024 AN: 86218

European-Finnish (FIN) AF: 0.327 AC: 17417 AN: 53290

Middle Eastern (MID) AF: 0.352 AC: 2032 AN: 5766

European-Non Finnish (NFE) AF: 0.371 AC: 412285 AN: 1111748

Other (OTH) AF: 0.349 AC: 21057 AN: 60380

GnomAD4 genome AF: 0.323 AC: 49005 AN: 151894 Hom.: 8348 Cov.: 31 AF XY: 0.321 AC XY: 23842 AN XY: 74234

African (AFR) AF: 0.214 AC: 8881 AN: 41404

American (AMR) AF: 0.403 AC: 6154 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1392 AN: 3464

East Asian (EAS) AF: 0.299 AC: 1540 AN: 5152

South Asian (SAS) AF: 0.281 AC: 1352 AN: 4810

European-Finnish (FIN) AF: 0.319 AC: 3370 AN: 10580

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25033 AN: 67904

Other (OTH) AF: 0.341 AC: 721 AN: 2112

Alfa AF: 0.356 Hom.: 33034

Bravo AF: 0.329

Asia WGS AF: 0.266 AC: 925 AN: 3478

EpiCase AF: 0.368

EpiControl AF: 0.372

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ATP2A3-related disorder Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.48
PhyloP100		1.5
Mutation Taster		=99/1	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: rs887387; hg19: chr17-3828702; COSMIC: COSV59225720; COSMIC: COSV59225720;