rs1553756062
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_ModeratePP5_Moderate
The NM_001378452.1(ITPR1):c.7352T>C(p.Leu2451Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
ITPR1
NM_001378452.1 missense
NM_001378452.1 missense
Scores
14
2
1
Clinical Significance
Conservation
PhyloP100: 7.92
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 Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, ITPR1
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.903
PP5
?
Variant 3-4811344-T-C is Pathogenic according to our data. Variant chr3-4811344-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 503525.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITPR1 | NM_001378452.1 | c.7352T>C | p.Leu2451Pro | missense_variant | 56/62 | ENST00000649015.2 | |
ITPR1 | NM_001168272.2 | c.7307T>C | p.Leu2436Pro | missense_variant | 55/61 | ||
ITPR1 | NM_001099952.4 | c.7208T>C | p.Leu2403Pro | missense_variant | 53/59 | ||
ITPR1 | NM_002222.7 | c.7163T>C | p.Leu2388Pro | missense_variant | 52/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITPR1 | ENST00000649015.2 | c.7352T>C | p.Leu2451Pro | missense_variant | 56/62 | NM_001378452.1 | |||
ENST00000693140.1 | n.581+14402A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Spinocerebellar ataxia type 29 Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Schule lab, Hertie Institute for Clinical Brain Research | Feb 09, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D;D;D;.;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.;D;.;N;.;.;.;D;.
REVEL
Pathogenic
Sift
Uncertain
D;D;.;D;.;D;.;.;.;D;.
Sift4G
Pathogenic
D;D;.;D;.;D;.;.;.;D;.
Polyphen
1.0
.;.;.;.;.;D;.;D;.;.;.
Vest4
MutPred
0.65
.;.;.;.;.;.;.;Loss of stability (P = 0.0152);.;.;.;
MVP
MPC
2.5
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at