16-30949371-C-T

Variant names:

• chr16-30949371-C-T
• rs773401498
• NM_152288.3:c.82C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152288.3(ORAI3):​c.82C>T​(p.Arg28Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,420,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ORAI3 NM_152288.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20

Genes affected

ORAI3 (HGNC:28185): (ORAI calcium release-activated calcium modulator 3) Predicted to enable store-operated calcium channel activity. Predicted to be involved in store-operated calcium entry. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000261487 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.764

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORAI3	NM_152288.3	c.82C>T	p.Arg28Trp	missense_variant	Exon 1 of 2	ENST00000318663.5	NP_689501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORAI3	ENST00000318663.5	c.82C>T	p.Arg28Trp	missense_variant	Exon 1 of 2	1	NM_152288.3	ENSP00000322249.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000561 AC: 1 AN: 178176 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 98592

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000397

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1420012 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 703526

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.15e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	T;T;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.29	D
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	N;.;.
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.78
MutPred		0.39		Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);Loss of disorder (P = 0.0055);
MVP		0.59
MPC		0.69
ClinPred		0.96	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.23
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs773401498; hg19: chr16-30960692;