chr17-3943508-A-G

Variant names:

• chr17-3943508-A-G
• rs758641
• NM_005173.4:c.1302T>C

Variant summary

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

The NM_174953.3(ATP2A3):​c.1302T>C​(p.Tyr434Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,613,542 control chromosomes in the GnomAD database, including 149,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.41 (13315 hom., cov: 31)
  • Exomes 𝑓: 0.42 (136068 hom.)
• Consequence: ATP2A3 NM_174953.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.116
• Publications: 21 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=-0.66).
• BP6: Variant 17-3943508-A-G is Benign according to our data. Variant chr17-3943508-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059760.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.116 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174953.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2A3	NM_005173.4	MANE Select	c.1302T>C	p.Tyr434Tyr	synonymous	Exon 11 of 21	NP_005164.2
	ATP2A3	NM_174953.3		c.1302T>C	p.Tyr434Tyr	synonymous	Exon 11 of 23	NP_777613.1
	ATP2A3	NM_174954.3		c.1302T>C	p.Tyr434Tyr	synonymous	Exon 11 of 23	NP_777614.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2A3	ENST00000397041.8	TSL:1 MANE Select	c.1302T>C	p.Tyr434Tyr	synonymous	Exon 11 of 21	ENSP00000380234.3
	ATP2A3	ENST00000397043.7	TSL:1	c.1302T>C	p.Tyr434Tyr	synonymous	Exon 11 of 21	ENSP00000380236.3
	ATP2A3	ENST00000359983.7	TSL:5	c.1302T>C	p.Tyr434Tyr	synonymous	Exon 11 of 23	ENSP00000353072.3

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62078 AN: 151730 Hom.: 13298 Cov.: 31

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.0832

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.437

GnomAD2 exomes AF: 0.397 AC: 99922 AN: 251406 AF XY: 0.398

Gnomad AFR exome AF: 0.379

Gnomad AMR exome AF: 0.437

Gnomad ASJ exome AF: 0.578

Gnomad EAS exome AF: 0.0793

Gnomad FIN exome AF: 0.328

Gnomad NFE exome AF: 0.456

Gnomad OTH exome AF: 0.434

GnomAD4 exome AF: 0.425 AC: 620526 AN: 1461694 Hom.: 136068 Cov.: 67 AF XY: 0.423 AC XY: 307315 AN XY: 727164

African (AFR) AF: 0.376 AC: 12596 AN: 33478

American (AMR) AF: 0.437 AC: 19535 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 14885 AN: 26130

East Asian (EAS) AF: 0.0710 AC: 2818 AN: 39696

South Asian (SAS) AF: 0.318 AC: 27404 AN: 86256

European-Finnish (FIN) AF: 0.334 AC: 17853 AN: 53376

Middle Eastern (MID) AF: 0.495 AC: 2853 AN: 5768

European-Non Finnish (NFE) AF: 0.447 AC: 497233 AN: 1111886

Other (OTH) AF: 0.420 AC: 25349 AN: 60386

GnomAD4 genome AF: 0.409 AC: 62140 AN: 151848 Hom.: 13315 Cov.: 31 AF XY: 0.404 AC XY: 29950 AN XY: 74208

African (AFR) AF: 0.381 AC: 15766 AN: 41412

American (AMR) AF: 0.459 AC: 7018 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2048 AN: 3470

East Asian (EAS) AF: 0.0827 AC: 426 AN: 5154

South Asian (SAS) AF: 0.306 AC: 1475 AN: 4822

European-Finnish (FIN) AF: 0.322 AC: 3390 AN: 10524

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.450 AC: 30555 AN: 67886

Other (OTH) AF: 0.433 AC: 908 AN: 2098

Alfa AF: 0.439 Hom.: 19346

Bravo AF: 0.417

Asia WGS AF: 0.207 AC: 722 AN: 3478

EpiCase AF: 0.464

EpiControl AF: 0.462

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ATP2A3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.0
DANN	Benign	0.37
PhyloP100		-0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=292/8	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: rs758641; hg19: chr17-3846802; COSMIC: COSV59227357;