chr17-3925408-T-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000572116.1(ATP2A3):​c.399A>T​(p.Arg133Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R133R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ATP2A3 ENST00000572116.1 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1232554).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2A3	NM_005173.4	MANE Select	c.*14A>T		3_prime_UTR	Exon 21 of 21	NP_005164.2
	ATP2A3	NM_174955.3		c.3102A>T	p.Arg1034Ser	missense	Exon 22 of 22	NP_777615.1
	ATP2A3	NM_174953.3		c.*14A>T		3_prime_UTR	Exon 23 of 23	NP_777613.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2A3	ENST00000572116.1	TSL:1	c.399A>T	p.Arg133Ser	missense	Exon 5 of 5	ENSP00000458865.1
	ATP2A3	ENST00000397041.8	TSL:1 MANE Select	c.*14A>T		3_prime_UTR	Exon 21 of 21	ENSP00000380234.3
	ATP2A3	ENST00000397043.7	TSL:1	c.*14A>T		3_prime_UTR	Exon 21 of 21	ENSP00000380236.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 33034

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.088	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.49	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.12	T
MetaSVM	Uncertain	0.11	D
MutationAssessor	Benign	0.0	N
PhyloP100		1.5
PROVEAN	Benign	0.29	N
REVEL	Benign	0.17
Sift	Benign	0.076	T
Sift4G	Benign	0.58	T
Polyphen		0.42	B
Vest4		0.28
MutPred		0.13		Gain of phosphorylation at R1034 (P = 0.0434)
MVP		0.60
ClinPred		0.069	T
GERP RS		3.4
Varity_R		0.18

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;