rs753499808
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_001378452.1(ITPR1):c.7042A>G(p.Thr2348Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,706 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
Consequence
NM_001378452.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ITPR1 | NM_001378452.1 | c.7042A>G | p.Thr2348Ala | missense_variant | Exon 54 of 62 | ENST00000649015.2 | NP_001365381.1 | |
ITPR1 | NM_001168272.2 | c.6997A>G | p.Thr2333Ala | missense_variant | Exon 53 of 61 | NP_001161744.1 | ||
ITPR1 | NM_001099952.4 | c.6898A>G | p.Thr2300Ala | missense_variant | Exon 51 of 59 | NP_001093422.2 | ||
ITPR1 | NM_002222.7 | c.6853A>G | p.Thr2285Ala | missense_variant | Exon 50 of 58 | NP_002213.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ITPR1 | ENST00000649015.2 | c.7042A>G | p.Thr2348Ala | missense_variant | Exon 54 of 62 | NM_001378452.1 | ENSP00000497605.1 | |||
ITPR1 | ENST00000354582.12 | c.7018A>G | p.Thr2340Ala | missense_variant | Exon 54 of 62 | 5 | ENSP00000346595.8 | |||
ITPR1 | ENST00000648266.1 | c.7015A>G | p.Thr2339Ala | missense_variant | Exon 54 of 62 | ENSP00000498014.1 | ||||
ITPR1 | ENST00000650294.1 | c.7000A>G | p.Thr2334Ala | missense_variant | Exon 53 of 61 | ENSP00000498056.1 | ||||
ITPR1 | ENST00000443694.5 | c.6997A>G | p.Thr2333Ala | missense_variant | Exon 53 of 61 | 1 | ENSP00000401671.2 | |||
ITPR1 | ENST00000648309.1 | c.6970A>G | p.Thr2324Ala | missense_variant | Exon 51 of 59 | ENSP00000497026.1 | ||||
ITPR1 | ENST00000357086.10 | c.6898A>G | p.Thr2300Ala | missense_variant | Exon 51 of 59 | 1 | ENSP00000349597.4 | |||
ITPR1 | ENST00000456211.8 | c.6853A>G | p.Thr2285Ala | missense_variant | Exon 50 of 58 | 1 | ENSP00000397885.2 | |||
ITPR1 | ENST00000648038.1 | c.4804A>G | p.Thr1602Ala | missense_variant | Exon 34 of 42 | ENSP00000497872.1 | ||||
ITPR1 | ENST00000648431.1 | c.4219A>G | p.Thr1407Ala | missense_variant | Exon 31 of 39 | ENSP00000498149.1 | ||||
ITPR1 | ENST00000648212.1 | c.3982A>G | p.Thr1328Ala | missense_variant | Exon 31 of 39 | ENSP00000498022.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249270Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135240
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461706Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727136
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:2
ClinVar contains an entry for this variant (Variation ID: 586054). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ITPR1 protein function. This variant has not been reported in the literature in individuals affected with ITPR1-related conditions. This variant is present in population databases (rs753499808, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 2285 of the ITPR1 protein (p.Thr2285Ala). -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at