rs374078983

Variant names:

• chr17-3929444-C-A
• rs374078983
• NM_005173.4:c.2746G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-3929444-C-A
• chr17-3929444-C-G
• chr17-3929444-C-T

Variant summary

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

The NM_005173.4(ATP2A3):​c.2746G>T​(p.Val916Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,438,572 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ATP2A3 NM_005173.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001139
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2A3	NM_005173.4	c.2746G>T	p.Val916Phe	missense_variant, splice_region_variant	Exon 19 of 21	ENST00000397041.8	NP_005164.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP2A3	ENST00000397041.8	c.2746G>T	p.Val916Phe	missense_variant, splice_region_variant	Exon 19 of 21	1	NM_005173.4	ENSP00000380234.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1438572 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 713738

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: 0.00

Gnomad4 NFE exome AF: 9.08e-7

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	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.73	.;.;.;.;.;D;.;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.26	N
LIST_S2	Uncertain	0.95	D;D;.;D;D;D;D;D
M_CAP	Pathogenic	0.65	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.85	D
MutationAssessor	Uncertain	2.4	M;M;M;.;M;M;M;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.1	N;N;N;.;N;N;N;.
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0010	D;D;D;.;D;D;D;.
Sift4G	Uncertain	0.0080	D;D;D;D;D;D;D;D
Polyphen		0.70	P;P;P;.;.;P;P;.
Vest4		0.67
MutPred		0.60		Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);.;Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);.;
MVP		0.90
MPC		1.4
ClinPred		0.97	D
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.42
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.030
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

Publications

LitVar

Other links and lift over

dbSNP: rs374078983; hg19: chr17-3832738;