chr6-33668883-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002224.4(ITPR3):​c.2007-91C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ITPR3
NM_002224.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.93

Publications

15 publications found
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]
ITPR3 Gene-Disease associations (from GenCC):
  • Charcot-Marie-Tooth disease, demyelinating, type 1J
    Inheritance: AD Classification: DEFINITIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ITPR3NM_002224.4 linkc.2007-91C>A intron_variant Intron 17 of 57 ENST00000605930.3 NP_002215.2 Q14573A6H8K3Q59ES2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITPR3ENST00000605930.3 linkc.2007-91C>A intron_variant Intron 17 of 57 1 NM_002224.4 ENSP00000475177.1 Q14573
ITPR3ENST00000374316.9 linkc.2007-91C>A intron_variant Intron 18 of 58 5 ENSP00000363435.4 Q14573

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1222282
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
609198
African (AFR)
AF:
0.00
AC:
0
AN:
28650
American (AMR)
AF:
0.00
AC:
0
AN:
34522
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
21022
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37266
South Asian (SAS)
AF:
0.00
AC:
0
AN:
71028
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
41508
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4908
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
931284
Other (OTH)
AF:
0.00
AC:
0
AN:
52094
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.097
DANN
Benign
0.50
PhyloP100
-1.9

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

Other links and lift over

dbSNP: rs2296336; hg19: chr6-33636660; API