17-3929420-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_005173.4(ATP2A3):c.2770C>T(p.Arg924Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,593,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 0 hom. )
Consequence
ATP2A3
NM_005173.4 missense
NM_005173.4 missense
Scores
6
9
3
Clinical Significance
Conservation
PhyloP100: 3.19
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.16048807).
BP6
?
Variant 17-3929420-G-A is Benign according to our data. Variant chr17-3929420-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 757608.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP2A3 | NM_005173.4 | c.2770C>T | p.Arg924Trp | missense_variant | 19/21 | ENST00000397041.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP2A3 | ENST00000397041.8 | c.2770C>T | p.Arg924Trp | missense_variant | 19/21 | 1 | NM_005173.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000283 AC: 43AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000240 AC: 51AN: 212300Hom.: 0 AF XY: 0.000165 AC XY: 19AN XY: 114868
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GnomAD4 exome AF: 0.000170 AC: 245AN: 1441016Hom.: 0 Cov.: 31 AF XY: 0.000141 AC XY: 101AN XY: 715132
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GnomAD4 genome ? AF: 0.000282 AC: 43AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28AN XY: 74466
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 09, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;.;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M;M;.;M;M;M;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;.;D;D;D;.
REVEL
Pathogenic
Sift
Uncertain
D;D;D;.;D;D;D;.
Sift4G
Uncertain
D;D;D;D;D;D;D;D
Polyphen
D;D;D;.;.;D;D;.
Vest4
MVP
MPC
1.5
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at