chr1-203683356-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001684.5(ATP2B4):c.151G>A(p.Val51Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,784 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
ATP2B4
NM_001684.5 missense
NM_001684.5 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 4.76
Genes affected
ATP2B4 (HGNC:817): (ATPase plasma membrane Ca2+ transporting 4) 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 4. 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 Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP2B4 | NM_001684.5 | c.151G>A | p.Val51Ile | missense_variant | 2/21 | ENST00000357681.10 | |
ATP2B4 | NM_001001396.3 | c.151G>A | p.Val51Ile | missense_variant | 2/22 | ||
ATP2B4 | NM_001365783.2 | c.151G>A | p.Val51Ile | missense_variant | 2/21 | ||
ATP2B4 | NM_001365784.2 | c.151G>A | p.Val51Ile | missense_variant | 2/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP2B4 | ENST00000357681.10 | c.151G>A | p.Val51Ile | missense_variant | 2/21 | 1 | NM_001684.5 | A1 | |
ATP2B4 | ENST00000341360.7 | c.151G>A | p.Val51Ile | missense_variant | 2/22 | 1 | P4 | ||
ATP2B4 | ENST00000705901.1 | c.151G>A | p.Val51Ile | missense_variant | 2/21 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461584Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727088
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152200Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1AN XY: 74356
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 21, 2021 | The c.151G>A (p.V51I) alteration is located in exon 2 (coding exon 1) of the ATP2B4 gene. This alteration results from a G to A substitution at nucleotide position 151, causing the valine (V) at amino acid position 51 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L;L
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at