rs786204796
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_032790.3(ORAI1):c.295G>A(p.Gly99Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
ORAI1
NM_032790.3 missense
NM_032790.3 missense
Scores
9
5
1
Clinical Significance
Conservation
PhyloP100: 9.67
Genes affected
ORAI1 (HGNC:25896): (ORAI calcium release-activated calcium modulator 1) The protein encoded by this gene is a membrane calcium channel subunit that is activated by the calcium sensor STIM1 when calcium stores are depleted. This type of channel is the primary way for calcium influx into T-cells. Defects in this gene are a cause of immune dysfunction with T-cell inactivation due to calcium entry defect type 1 (IDTICED1). [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.956
PP5
?
Variant 12-121627039-G-A is Pathogenic according to our data. Variant chr12-121627039-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 189256.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ORAI1 | NM_032790.3 | c.295G>A | p.Gly99Ser | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ORAI1 | ENST00000617316.2 | c.292G>A | p.Gly98Ser | missense_variant | 2/3 | 1 | P1 | ||
ORAI1 | ENST00000611718.1 | n.224G>A | non_coding_transcript_exon_variant | 1/2 | 5 | ||||
ORAI1 | ENST00000646827.1 | n.490G>A | non_coding_transcript_exon_variant | 1/2 | |||||
ORAI1 | ENST00000698901.1 | n.425+106G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Myopathy, tubular aggregate, 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2015 | - - |
Myopathy with tubular aggregates Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Muscle and Diseases Team, Institut de Génétique et Biologie Moléculaire et Cellulaire | Mar 01, 2024 | PS3+PM2+PM6+PP3+PP4 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
Polyphen
D
MutPred
Gain of catalytic residue at A100 (P = 0.0125);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at