12-121626873-C-CCCGCCA
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_032790.3(ORAI1):c.135_140dup(p.Pro47_Pro48dup) variant causes a inframe insertion, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 31)
Consequence
ORAI1
NM_032790.3 inframe_insertion, splice_region
NM_032790.3 inframe_insertion, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.158
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 Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_032790.3.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ORAI1 | NM_032790.3 | c.135_140dup | p.Pro47_Pro48dup | inframe_insertion, splice_region_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ORAI1 | ENST00000617316.2 | c.132_137dup | p.Pro46_Pro47dup | inframe_insertion | 2/3 | 1 | P1 | ||
ORAI1 | ENST00000611718.1 | n.64_69dup | non_coding_transcript_exon_variant | 1/2 | 5 | ||||
ORAI1 | ENST00000646827.1 | n.330_335dup | non_coding_transcript_exon_variant | 1/2 | |||||
ORAI1 | ENST00000698901.1 | n.371_376dup | non_coding_transcript_exon_variant | 1/2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Combined immunodeficiency due to ORAI1 deficiency;C4014557:Myopathy, tubular aggregate, 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 13, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at