NM_005173.4:c.2894G>T

Variant names:

• chr17-3928749-C-A
• NM_005173.4:c.2894G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005173.4(ATP2A3):​c.2894G>T​(p.Arg965Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ATP2A3 NM_005173.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.115627736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2A3	NM_005173.4	c.2894G>T	p.Arg965Leu	missense_variant	Exon 20 of 21	ENST00000397041.8	NP_005164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2A3	ENST00000397041.8	c.2894G>T	p.Arg965Leu	missense_variant	Exon 20 of 21	1	NM_005173.4	ENSP00000380234.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400592 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 691024

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000205

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	.;.;.;.;.;T;.;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.20	N
LIST_S2	Uncertain	0.92	D;D;.;D;D;D;D;D
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.12	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.031	D
MutationAssessor	Benign	-0.18	N;N;N;.;N;N;N;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.42	N;N;N;.;N;N;N;.
REVEL	Uncertain	0.38
Sift	Benign	0.34	T;T;T;.;T;T;T;.
Sift4G	Benign	0.35	T;T;T;T;T;T;T;T
Polyphen		0.0010	B;B;B;.;.;B;B;.
Vest4		0.21
MutPred		0.40		Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);.;Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);.;
MVP		0.65
MPC		2.4
ClinPred		0.48	T
GERP RS		0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.074
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-3832043;