chr17-3929444-C-G

Variant names:

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

Variant summary

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

The NM_005173.4(ATP2A3):​c.2746G>C​(p.Val916Leu) variant causes a missense, splice region 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. 17/23 in silico tools predict a benign outcome for this variant. 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)
• Consequence: ATP2A3 NM_005173.4 missense, splice_region
• Scores: Splicing: ADA: 0.0001009
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.110394925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP2A3	NM_005173.4	c.2746G>C	p.Val916Leu	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>C	p.Val916Leu	missense_variant, splice_region_variant	Exon 19 of 21	1	NM_005173.4	ENSP00000380234.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	0.0045	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	11
DANN	Benign	0.25
DEOGEN2	Benign	0.42	.;.;.;.;.;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.79	T;T;.;T;T;T;T;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.11	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	-1.7	N;N;N;.;N;N;N;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	1.3	N;N;N;.;N;N;N;.
REVEL	Benign	0.27
Sift	Benign	1.0	T;T;T;.;T;T;T;.
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T
Polyphen		0.0	B;B;B;.;.;B;B;.
Vest4		0.25
MutPred		0.55		Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;
MVP		0.61
MPC		0.53
ClinPred		0.064	T
GERP RS		2.7
Varity_R		0.042
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.062
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;