rs11963294

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The ENST00000605930.3(ITPR3):​c.2000G>A​(p.Arg667Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000167 in 1,614,054 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ITPR3
ENST00000605930.3 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.79
Variant links:
Genes affected
ITPR3 (HGNC:6182): (inositol 1,4,5-trisphosphate receptor type 3) This gene encodes a receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. The receptor contains a calcium channel at the C-terminus and the ligand-binding site at the N-terminus. Knockout studies in mice suggest that type 2 and type 3 inositol 1,4,5-trisphosphate receptors play a key role in exocrine secretion underlying energy metabolism and growth. [provided by RefSeq, Aug 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ITPR3. . Gene score misZ 4.5522 (greater than the threshold 3.09). Trascript score misZ 5.2589 (greater than threshold 3.09). GenCC has associacion of gene with Charcot-Marie-Tooth disease, demyelinating, type 1J.
BP4
Computational evidence support a benign effect (MetaRNN=0.15626404).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ITPR3NM_002224.4 linkuse as main transcriptc.2000G>A p.Arg667Gln missense_variant 17/58 ENST00000605930.3 NP_002215.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ITPR3ENST00000605930.3 linkuse as main transcriptc.2000G>A p.Arg667Gln missense_variant 17/581 NM_002224.4 ENSP00000475177 P1
ITPR3ENST00000374316.9 linkuse as main transcriptc.2000G>A p.Arg667Gln missense_variant 18/595 ENSP00000363435 P1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152202
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000477
AC:
12
AN:
251364
Hom.:
0
AF XY:
0.0000589
AC XY:
8
AN XY:
135880
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000150
AC:
22
AN:
1461852
Hom.:
0
Cov.:
34
AF XY:
0.0000193
AC XY:
14
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152202
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000337
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.0000741
AC:
9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.049
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
15
DANN
Benign
0.89
DEOGEN2
Uncertain
0.47
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.36
N
LIST_S2
Benign
0.86
.;D
M_CAP
Benign
0.038
D
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-0.64
T
MutationAssessor
Benign
-1.1
N;N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
2.1
N;.
REVEL
Benign
0.27
Sift
Benign
0.46
T;.
Sift4G
Benign
0.46
T;T
Polyphen
0.0010
B;B
Vest4
0.076
MVP
0.70
MPC
0.47
ClinPred
0.039
T
GERP RS
0.38
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.032
gMVP
0.094

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11963294; hg19: chr6-33636405; API