Genetic Variant NM_152288.3:c.116T>C (chr16-30949405-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152288.3(ORAI3):c.116T>C(p.Met39Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000621 in 1,448,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ORAI3
NM_152288.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.05

Publications

0 publications found

Variant links:

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]

ORAI3 links:

ENSG00000261487 (HGNC:):

ENSG00000261487 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25272635).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152288.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ORAI3	NM_152288.3	MANE Select	c.116T>C	p.Met39Thr	missense	Exon 1 of 2	NP_689501.1	Q9BRQ5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ORAI3	ENST00000318663.5	TSL:1 MANE Select	c.116T>C	p.Met39Thr	missense	Exon 1 of 2	ENSP00000322249.4	Q9BRQ5
ORAI3	ENST00000566237.1	TSL:5	c.116T>C	p.Met39Thr	missense	Exon 1 of 3	ENSP00000457388.1	H3BTY7
ORAI3	ENST00000562699.1	TSL:2	c.116T>C	p.Met39Thr	missense	Exon 1 of 2	ENSP00000457025.1	H3BT51

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

216626

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000621

AC:

AN:

1448426

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

719802

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33042

American (AMR)

AF:

0.00

AC:

AN:

43486

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25788

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38866

South Asian (SAS)

AF:

0.00

AC:

AN:

84380

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5564

European-Non Finnish (NFE)

AF:

0.00000723

AC:

AN:

1107098

Other (OTH)

AF:

0.00

AC:

AN:

59796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000837

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.060

Eigen

Benign

0.086

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.74

M_CAP

Benign

0.076

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

6.1

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.25

REVEL

Benign

0.26

Sift

Benign

0.053

Sift4G

Benign

0.26

Polyphen

0.82

Vest4

0.52

MVP

0.092

MPC

0.20

ClinPred

0.92

GERP RS

5.3

PromoterAI

-0.039

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.51

gMVP

0.32

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over