rs1006793896

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001366521.1(ATP2B1):​c.3541C>G​(p.Pro1181Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1181H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

ATP2B1
NM_001366521.1 missense

Scores

2
5
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.72
Variant links:
Genes affected
ATP2B1 (HGNC:814): (ATPase plasma membrane Ca2+ transporting 1) The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis. The mammalian plasma membrane calcium ATPase isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts. The expression of different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 1. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

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=0.17700574).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATP2B1NM_001366521.1 linkc.3541C>G p.Pro1181Ala missense_variant Exon 21 of 21 ENST00000428670.8 NP_001353450.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATP2B1ENST00000428670.8 linkc.3541C>G p.Pro1181Ala missense_variant Exon 21 of 21 5 NM_001366521.1 ENSP00000392043.3 P20020-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461150
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726900
show subpopulations
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:
9.00e-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
Benign
0.054
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Benign
22
DANN
Benign
0.95
DEOGEN2
Benign
0.020
.;.;T
Eigen
Benign
0.033
Eigen_PC
Benign
0.22
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.69
T;.;T
M_CAP
Benign
0.061
D
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Uncertain
0.29
D
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-1.5
N;N;N
REVEL
Uncertain
0.44
Sift
Benign
0.045
D;D;D
Sift4G
Uncertain
0.052
T;T;T
Vest4
0.26
MutPred
0.18
Gain of catalytic residue at P1179 (P = 0.001);Gain of catalytic residue at P1179 (P = 0.001);.;
MVP
0.43
MPC
0.047
ClinPred
0.92
D
GERP RS
5.4
Varity_R
0.13
gMVP
0.55

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-89984883; API