rs535969136
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001378452.1(ITPR1):c.5789C>A(p.Ala1930Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,976 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: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
ITPR1
NM_001378452.1 missense
NM_001378452.1 missense
Scores
5
8
6
Clinical Significance
Conservation
PhyloP100: 1.98
Genes affected
ITPR1 (HGNC:6180): (inositol 1,4,5-trisphosphate receptor type 1) This gene encodes an intracellular receptor for inositol 1,4,5-trisphosphate. Upon stimulation by inositol 1,4,5-trisphosphate, this receptor mediates calcium release from the endoplasmic reticulum. Mutations in this gene cause spinocerebellar ataxia type 15, a disease associated with an heterogeneous group of cerebellar disorders. Multiple transcript variants have been identified for this gene. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ITPR1. . Gene score misZ: 5.5951 (greater than the threshold 3.09). Trascript score misZ: 6.2026 (greater than threshold 3.09). The gene has 44 curated pathogenic missense variants (we use a threshold of 10). The gene has 31 curated benign missense variants. GenCC has associacion of the gene with spinocerebellar ataxia type 15/16, aniridia-cerebellar ataxia-intellectual disability syndrome, spinocerebellar ataxia type 29.
BP4
Computational evidence support a benign effect (MetaRNN=0.38073987).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ITPR1 | NM_001378452.1 | c.5789C>A | p.Ala1930Asp | missense_variant | 46/62 | ENST00000649015.2 | NP_001365381.1 | |
ITPR1 | NM_001168272.2 | c.5744C>A | p.Ala1915Asp | missense_variant | 45/61 | NP_001161744.1 | ||
ITPR1 | NM_001099952.4 | c.5645C>A | p.Ala1882Asp | missense_variant | 43/59 | NP_001093422.2 | ||
ITPR1 | NM_002222.7 | c.5600C>A | p.Ala1867Asp | missense_variant | 42/58 | NP_002213.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ITPR1 | ENST00000649015.2 | c.5789C>A | p.Ala1930Asp | missense_variant | 46/62 | NM_001378452.1 | ENSP00000497605.1 | |||
ITPR1 | ENST00000354582.12 | c.5765C>A | p.Ala1922Asp | missense_variant | 46/62 | 5 | ENSP00000346595.8 | |||
ITPR1 | ENST00000648266.1 | c.5762C>A | p.Ala1921Asp | missense_variant | 46/62 | ENSP00000498014.1 | ||||
ITPR1 | ENST00000650294.1 | c.5747C>A | p.Ala1916Asp | missense_variant | 45/61 | ENSP00000498056.1 | ||||
ITPR1 | ENST00000443694.5 | c.5744C>A | p.Ala1915Asp | missense_variant | 45/61 | 1 | ENSP00000401671.2 | |||
ITPR1 | ENST00000648309.1 | c.5717C>A | p.Ala1906Asp | missense_variant | 43/59 | ENSP00000497026.1 | ||||
ITPR1 | ENST00000357086.10 | c.5645C>A | p.Ala1882Asp | missense_variant | 43/59 | 1 | ENSP00000349597.4 | |||
ITPR1 | ENST00000456211.8 | c.5600C>A | p.Ala1867Asp | missense_variant | 42/58 | 1 | ENSP00000397885.2 | |||
ITPR1 | ENST00000648038.1 | c.3551C>A | p.Ala1184Asp | missense_variant | 26/42 | ENSP00000497872.1 | ||||
ITPR1 | ENST00000648431.1 | c.3089C>A | p.Ala1030Asp | missense_variant | 24/39 | ENSP00000498149.1 | ||||
ITPR1 | ENST00000648212.1 | c.2696C>A | p.Ala899Asp | missense_variant | 22/39 | ENSP00000498022.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152180Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249084Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135148
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461678Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727122
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74478
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Nov 20, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
.;.;.;.;.;.;D;.;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D;D;.;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;.;.;.;.;.;M;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;.;D;.;.;.;.;D;.
REVEL
Pathogenic
Sift
Benign
T;T;.;T;.;.;.;.;T;.
Sift4G
Benign
T;T;.;T;.;.;.;.;T;.
Polyphen
0.41
.;.;.;.;.;.;B;.;.;.
Vest4
MutPred
0.34
.;.;.;.;.;.;Loss of MoRF binding (P = 0.061);.;.;.;
MVP
MPC
0.54
ClinPred
D
GERP RS
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at