rs141235119

Variant names:

• chr17-3930371-C-G
• rs141235119
• NM_005173.4:c.2674G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-3930371-C-G
• chr17-3930371-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_005173.4(ATP2A3):​c.2674G>C​(p.Glu892Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000351 in 1,613,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E892K) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00036 (0 hom.)
• Consequence: ATP2A3 NM_005173.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17
• Publications: 8 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.4145764).

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.2674G>C	p.Glu892Gln	missense	Exon 18 of 21	NP_005164.2
	ATP2A3	NM_174953.3		c.2674G>C	p.Glu892Gln	missense	Exon 18 of 23	NP_777613.1	Q93084-5
	ATP2A3	NM_174954.3		c.2674G>C	p.Glu892Gln	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.2674G>C	p.Glu892Gln	missense	Exon 18 of 21	ENSP00000380234.3	Q93084-2
	ATP2A3	ENST00000397043.7	TSL:1	c.2674G>C	p.Glu892Gln	missense	Exon 18 of 21	ENSP00000380236.3	Q93084-4
	ATP2A3	ENST00000570845.5	TSL:1	c.1G>C	p.Glu1Gln	missense	Exon 1 of 6	ENSP00000461480.1	A0A0C4DGN3

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152250 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000273 AC: 68 AN: 249296 AF XY: 0.000318

Gnomad AFR exome AF: 0.0000625

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000467

Gnomad NFE exome AF: 0.000382

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000358 AC: 523 AN: 1461372 Hom.: 0 Cov.: 33 AF XY: 0.000370 AC XY: 269 AN XY: 726946

African (AFR) AF: 0.000120 AC: 4 AN: 33470

American (AMR) AF: 0.000291 AC: 13 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.000279 AC: 24 AN: 86156

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53292

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000415 AC: 461 AN: 1111846

Other (OTH) AF: 0.000298 AC: 18 AN: 60374

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152368 Hom.: 0 Cov.: 31 AF XY: 0.000268 AC XY: 20 AN XY: 74508

African (AFR) AF: 0.0000962 AC: 4 AN: 41588

American (AMR) AF: 0.000719 AC: 11 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 4

Bravo AF: 0.000363

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.000239 AC: 29

EpiCase AF: 0.000654

EpiControl AF: 0.000653

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	0.00098	T
BayesDel_noAF	Uncertain	0.080
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.096
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	-0.021	T
MutationAssessor	Benign	1.3	L
PhyloP100		6.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.55
Sift	Benign	0.15	T
Sift4G	Benign	0.40	T
Polyphen		0.0010	B
Vest4		0.75
MVP		0.61
MPC		0.90
ClinPred		0.041	T
GERP RS		3.8
PromoterAI		-0.0054	Neutral
Varity_R		0.27
gMVP		0.87
Mutation Taster		=39/61	disease causing

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: rs141235119; hg19: chr17-3833665;