ENST00000572116.1:c.404A>G

Variant names:

• chr17-3925403-T-C
• rs79980163
• ENST00000572116.1:c.404A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The ENST00000572116.1(ATP2A3):​c.404A>G​(p.Glu135Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000631 in 1,613,864 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0032 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (4 hom.)
• Consequence: ATP2A3 ENST00000572116.1 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.333
• Publications: 1 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00803557).
• BP6: Variant 17-3925403-T-C is Benign according to our data. Variant chr17-3925403-T-C is described in ClinVar as Benign. ClinVar VariationId is 3040838.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000572116.1. 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.*19A>G		3_prime_UTR	Exon 21 of 21	NP_005164.2
	ATP2A3	NM_174955.3		c.3107A>G	p.Glu1036Gly	missense	Exon 22 of 22	NP_777615.1	Q93084-1
	ATP2A3	NM_174953.3		c.*19A>G		3_prime_UTR	Exon 23 of 23	NP_777613.1	Q93084-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2A3	ENST00000572116.1	TSL:1	c.404A>G	p.Glu135Gly	missense	Exon 5 of 5	ENSP00000458865.1	A0A0C4DGN1
	ATP2A3	ENST00000397041.8	TSL:1 MANE Select	c.*19A>G		3_prime_UTR	Exon 21 of 21	ENSP00000380234.3	Q93084-2
	ATP2A3	ENST00000397043.7	TSL:1	c.*19A>G		3_prime_UTR	Exon 21 of 21	ENSP00000380236.3	Q93084-4

Frequencies

GnomAD3 genomes AF: 0.00323 AC: 491 AN: 152060 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000923 AC: 231 AN: 250194 AF XY: 0.000606

Gnomad AFR exome AF: 0.0125

Gnomad AMR exome AF: 0.000637

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000532

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000361 AC: 527 AN: 1461686 Hom.: 4 Cov.: 30 AF XY: 0.000289 AC XY: 210 AN XY: 727150

African (AFR) AF: 0.0128 AC: 427 AN: 33480

American (AMR) AF: 0.000693 AC: 31 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111944

Other (OTH) AF: 0.000795 AC: 48 AN: 60390

GnomAD4 genome AF: 0.00323 AC: 491 AN: 152178 Hom.: 6 Cov.: 32 AF XY: 0.00309 AC XY: 230 AN XY: 74402

African (AFR) AF: 0.0113 AC: 468 AN: 41520

American (AMR) AF: 0.00118 AC: 18 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

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

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67970

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00110 Hom.: 3

Bravo AF: 0.00358

ESP6500AA AF: 0.0109 AC: 48

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00112 AC: 136

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.0000593

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	0.065
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.087	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0080	T
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.33
PROVEAN	Benign	0.15	N
REVEL	Benign	0.26
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.014	D
Polyphen		0.0	B
Vest4		0.071
MVP		0.57
ClinPred		0.0082	T
GERP RS		2.3
Varity_R		0.090
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs79980163; hg19: chr17-3828697;