3-4516546-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_001378452.1(ITPR1):c.55G>A(p.Ala19Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,452,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ITPR1 | NM_001378452.1 | c.55G>A | p.Ala19Thr | missense_variant | Exon 3 of 62 | ENST00000649015.2 | NP_001365381.1 | |
ITPR1 | NM_001168272.2 | c.55G>A | p.Ala19Thr | missense_variant | Exon 3 of 61 | NP_001161744.1 | ||
ITPR1 | NM_001099952.4 | c.55G>A | p.Ala19Thr | missense_variant | Exon 3 of 59 | NP_001093422.2 | ||
ITPR1 | NM_002222.7 | c.55G>A | p.Ala19Thr | missense_variant | Exon 3 of 58 | NP_002213.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ITPR1 | ENST00000649015.2 | c.55G>A | p.Ala19Thr | missense_variant | Exon 3 of 62 | NM_001378452.1 | ENSP00000497605.1 | |||
ITPR1 | ENST00000354582.12 | c.55G>A | p.Ala19Thr | missense_variant | Exon 3 of 62 | 5 | ENSP00000346595.8 | |||
ITPR1 | ENST00000648266.1 | c.55G>A | p.Ala19Thr | missense_variant | Exon 3 of 62 | ENSP00000498014.1 | ||||
ITPR1 | ENST00000650294.1 | c.55G>A | p.Ala19Thr | missense_variant | Exon 3 of 61 | ENSP00000498056.1 | ||||
ITPR1 | ENST00000443694.5 | c.55G>A | p.Ala19Thr | missense_variant | Exon 3 of 61 | 1 | ENSP00000401671.2 | |||
ITPR1 | ENST00000648309.1 | c.55G>A | p.Ala19Thr | missense_variant | Exon 1 of 59 | ENSP00000497026.1 | ||||
ITPR1 | ENST00000357086.10 | c.55G>A | p.Ala19Thr | missense_variant | Exon 3 of 59 | 1 | ENSP00000349597.4 | |||
ITPR1 | ENST00000456211.8 | c.55G>A | p.Ala19Thr | missense_variant | Exon 3 of 58 | 1 | ENSP00000397885.2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000414 AC: 1AN: 241762Hom.: 0 AF XY: 0.00000761 AC XY: 1AN XY: 131408
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1452774Hom.: 0 Cov.: 28 AF XY: 0.00000277 AC XY: 2AN XY: 722600
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 19 of the ITPR1 protein (p.Ala19Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with ITPR1-related conditions. 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. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at