ENST00000617316.2:c.*137_*138dupTT

Variant names:

• chr12-121641776-A-ATT
• rs35558190
• ENST00000617316.2:c.*137_*138dupTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000617316.2(ORAI1):​c.*137_*138dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000072 in 972,642 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: ORAI1 ENST00000617316.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 0 publications found

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]

ORAI1 Gene-Disease associations (from GenCC):

• tubular aggregate myopathy

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• myopathy, tubular aggregate, 2

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• combined immunodeficiency due to ORAI1 deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• Stormorken syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORAI1	NR_186857.1	n.1261_1262dupTT		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORAI1	ENST00000617316.2	c.*137_*138dupTT		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000482568.2
ORAI1	ENST00000646827.1	n.1241_1242dupTT		non_coding_transcript_exon_variant	Exon 2 of 2
ORAI1	ENST00000698901.2	n.1165_1166dupTT		non_coding_transcript_exon_variant	Exon 2 of 2
ORAI1	ENST00000611718.1	n.*243_*244insTT		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000720 AC: 7 AN: 972642 Hom.: 0 Cov.: 13 AF XY: 0.0000101 AC XY: 5 AN XY: 496686

African (AFR) AF: 0.00 AC: 0 AN: 23250

American (AMR) AF: 0.00 AC: 0 AN: 32548

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21368

East Asian (EAS) AF: 0.00 AC: 0 AN: 36014

South Asian (SAS) AF: 0.0000838 AC: 6 AN: 71570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3162

European-Non Finnish (NFE) AF: 0.00000142 AC: 1 AN: 705244

Other (OTH) AF: 0.00 AC: 0 AN: 43720

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35558190; hg19: chr12-122079682;