rs145840723

Variant names:

• chr16-30953612-C-A
• rs145840723
• NM_152288.3:c.656C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-30953612-C-A
• chr16-30953612-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152288.3(ORAI3):​c.656C>A​(p.Pro219Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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: 0.0000041 (0 hom.)
• Consequence: ORAI3 NM_152288.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12569275).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ORAI3	NM_152288.3	c.656C>A	p.Pro219Gln	missense_variant	Exon 2 of 2	ENST00000318663.5	NP_689501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ORAI3	ENST00000318663.5	c.656C>A	p.Pro219Gln	missense_variant	Exon 2 of 2	1	NM_152288.3	ENSP00000322249.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461860 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727240

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.4
DANN	Benign	0.94
DEOGEN2	Benign	0.19	T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.44	N;N
REVEL	Benign	0.068
Sift	Uncertain	0.022	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.31	B;.
Vest4		0.28
MutPred		0.22		Loss of glycosylation at P219 (P = 0.0241);Loss of glycosylation at P219 (P = 0.0241);
MVP		0.014
MPC		0.55
ClinPred		0.27	T
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.046
gMVP		0.51

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: rs145840723; hg19: chr16-30964933;