17-3930386-C-T

Variant names:

• chr17-3930386-C-T
• rs73330907
• NM_005173.4:c.2659G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_005173.4(ATP2A3):​c.2659G>A​(p.Asp887Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,613,848 control chromosomes in the GnomAD database, including 1,741 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.060 (892 hom., cov: 31)
  • Exomes 𝑓: 0.0062 (849 hom.)
• Consequence: ATP2A3 NM_005173.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.74
• Publications: 6 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029634237).
• BP6: Variant 17-3930386-C-T is Benign according to our data. Variant chr17-3930386-C-T is described in ClinVar as Benign. ClinVar VariationId is 3057024.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005173.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2A3	NM_005173.4	MANE Select	c.2659G>A	p.Asp887Asn	missense	Exon 18 of 21	NP_005164.2
	ATP2A3	NM_174953.3		c.2659G>A	p.Asp887Asn	missense	Exon 18 of 23	NP_777613.1	Q93084-5
	ATP2A3	NM_174954.3		c.2659G>A	p.Asp887Asn	missense	Exon 18 of 23	NP_777614.1	Q93084-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2A3	ENST00000397041.8	TSL:1 MANE Select	c.2659G>A	p.Asp887Asn	missense	Exon 18 of 21	ENSP00000380234.3	Q93084-2
	ATP2A3	ENST00000397043.7	TSL:1	c.2659G>A	p.Asp887Asn	missense	Exon 18 of 21	ENSP00000380236.3	Q93084-4
	ATP2A3	ENST00000359983.7	TSL:5	c.2659G>A	p.Asp887Asn	missense	Exon 18 of 23	ENSP00000353072.3	Q93084-5

Frequencies

GnomAD3 genomes AF: 0.0603 AC: 9171 AN: 152146 Hom.: 893 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.0388

GnomAD2 exomes AF: 0.0158 AC: 3950 AN: 249718 AF XY: 0.0113

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.0103

Gnomad ASJ exome AF: 0.0000999

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000497

Gnomad OTH exome AF: 0.00821

GnomAD4 exome AF: 0.00619 AC: 9049 AN: 1461584 Hom.: 849 Cov.: 33 AF XY: 0.00528 AC XY: 3839 AN XY: 727050

African (AFR) AF: 0.217 AC: 7262 AN: 33476

American (AMR) AF: 0.0121 AC: 541 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000348 AC: 30 AN: 86202

European-Finnish (FIN) AF: 0.0000563 AC: 3 AN: 53288

Middle Eastern (MID) AF: 0.00763 AC: 44 AN: 5768

European-Non Finnish (NFE) AF: 0.000336 AC: 374 AN: 1111940

Other (OTH) AF: 0.0132 AC: 795 AN: 60384

GnomAD4 genome AF: 0.0603 AC: 9182 AN: 152264 Hom.: 892 Cov.: 31 AF XY: 0.0571 AC XY: 4253 AN XY: 74460

African (AFR) AF: 0.209 AC: 8664 AN: 41528

American (AMR) AF: 0.0247 AC: 378 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000794 AC: 54 AN: 68030

Other (OTH) AF: 0.0384 AC: 81 AN: 2108

Alfa AF: 0.0240 Hom.: 776

Bravo AF: 0.0682

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.207 AC: 914

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.0194 AC: 2349

Asia WGS AF: 0.00924 AC: 33 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000652

ClinVar

ClinVar submissions

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
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	D
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.35
Sift	Benign	0.16	T
Sift4G	Benign	0.28	T
Polyphen		0.0010	B
Vest4		0.34
MPC		0.52
ClinPred		0.019	T
GERP RS		3.8
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.71
Mutation Taster		=93/7	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: rs73330907; hg19: chr17-3833680;