1-203698294-A-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001684.5(ATP2B4):c.331A>T(p.Ile111Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000132 in 152,076 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Consequence
ATP2B4
NM_001684.5 missense
NM_001684.5 missense
Scores
2
14
1
Clinical Significance
Conservation
PhyloP100: 3.60
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 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP2B4 | NM_001684.5 | c.331A>T | p.Ile111Phe | missense_variant | 3/21 | ENST00000357681.10 | |
ATP2B4 | NM_001001396.3 | c.331A>T | p.Ile111Phe | missense_variant | 3/22 | ||
ATP2B4 | NM_001365783.2 | c.331A>T | p.Ile111Phe | missense_variant | 3/21 | ||
ATP2B4 | NM_001365784.2 | c.331A>T | p.Ile111Phe | missense_variant | 3/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP2B4 | ENST00000357681.10 | c.331A>T | p.Ile111Phe | missense_variant | 3/21 | 1 | NM_001684.5 | A1 | |
ATP2B4 | ENST00000341360.7 | c.331A>T | p.Ile111Phe | missense_variant | 3/22 | 1 | P4 | ||
ATP2B4 | ENST00000705901.1 | c.331A>T | p.Ile111Phe | missense_variant | 3/21 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152076Hom.: 0 Cov.: 31
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GnomAD4 exome Cov.: 35
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 152076Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74276
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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 | Mar 06, 2023 | The c.331A>T (p.I111F) alteration is located in exon 3 (coding exon 2) of the ATP2B4 gene. This alteration results from a A to T substitution at nucleotide position 331, causing the isoleucine (I) at amino acid position 111 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
P;.;.
Vest4
MutPred
Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP
MPC
ClinPred
D
GERP RS
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