rs367814655

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_001378452.1(ITPR1):​c.255C>G​(p.Asp85Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,696 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

ITPR1
NM_001378452.1 missense

Scores

4
6
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.415
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the ITPR1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 44 curated pathogenic missense variants (we use a threshold of 10). The gene has 31 curated benign missense variants. Gene score misZ: 5.5951 (above the threshold of 3.09). Trascript score misZ: 6.2026 (above the threshold of 3.09). GenCC associations: The gene is linked to spinocerebellar ataxia type 15/16, aniridia-cerebellar ataxia-intellectual disability syndrome, spinocerebellar ataxia type 29.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ITPR1NM_001378452.1 linkc.255C>G p.Asp85Glu missense_variant Exon 5 of 62 ENST00000649015.2 NP_001365381.1
ITPR1NM_001168272.2 linkc.255C>G p.Asp85Glu missense_variant Exon 5 of 61 NP_001161744.1 Q14643-2
ITPR1NM_001099952.4 linkc.255C>G p.Asp85Glu missense_variant Exon 5 of 59 NP_001093422.2 Q14643-3B4DER3Q59H91
ITPR1NM_002222.7 linkc.255C>G p.Asp85Glu missense_variant Exon 5 of 58 NP_002213.5 Q14643-4B4DER3B4DGH1Q59H91

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITPR1ENST00000649015.2 linkc.255C>G p.Asp85Glu missense_variant Exon 5 of 62 NM_001378452.1 ENSP00000497605.1 Q14643-1
ITPR1ENST00000354582.12 linkc.255C>G p.Asp85Glu missense_variant Exon 5 of 62 5 ENSP00000346595.8 A0A3F2YNW8
ITPR1ENST00000648266.1 linkc.255C>G p.Asp85Glu missense_variant Exon 5 of 62 ENSP00000498014.1 A0A3B3IU04
ITPR1ENST00000650294.1 linkc.255C>G p.Asp85Glu missense_variant Exon 5 of 61 ENSP00000498056.1 A0A3B3ITU8
ITPR1ENST00000443694.5 linkc.255C>G p.Asp85Glu missense_variant Exon 5 of 61 1 ENSP00000401671.2 Q14643-2
ITPR1ENST00000648309.1 linkc.255C>G p.Asp85Glu missense_variant Exon 3 of 59 ENSP00000497026.1 Q14643-5
ITPR1ENST00000357086.10 linkc.255C>G p.Asp85Glu missense_variant Exon 5 of 59 1 ENSP00000349597.4 Q14643-3
ITPR1ENST00000456211.8 linkc.255C>G p.Asp85Glu missense_variant Exon 5 of 58 1 ENSP00000397885.2 Q14643-4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1460696
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
726660
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.63
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.070
CADD
Benign
0.010
DANN
Benign
0.93
DEOGEN2
Pathogenic
0.93
.;.;.;.;.;.;.;.;D;.;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.75
T;T;T;T;T;T;T;T;T;T;.
M_CAP
Uncertain
0.23
D
MetaRNN
Uncertain
0.74
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.65
D
MutationAssessor
Benign
1.7
L;L;.;.;L;.;.;.;L;L;L
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-2.8
D;D;.;D;D;.;N;.;.;.;D
REVEL
Uncertain
0.58
Sift
Benign
0.26
T;T;.;T;T;.;T;.;.;.;T
Sift4G
Benign
0.22
T;T;.;.;T;.;T;.;.;.;T
Polyphen
0.89, 0.0040
.;.;.;.;.;.;P;.;B;.;.
Vest4
0.80
MutPred
0.68
Gain of disorder (P = 0.161);Gain of disorder (P = 0.161);Gain of disorder (P = 0.161);Gain of disorder (P = 0.161);Gain of disorder (P = 0.161);Gain of disorder (P = 0.161);Gain of disorder (P = 0.161);Gain of disorder (P = 0.161);Gain of disorder (P = 0.161);Gain of disorder (P = 0.161);Gain of disorder (P = 0.161);
MVP
0.91
MPC
0.68
ClinPred
0.72
D
GERP RS
-8.4
Varity_R
0.27
gMVP
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-4669538; API