chr3-4800592-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS1
The NM_001378452.1(ITPR1):c.7099G>A(p.Ala2367Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000776 in 1,613,712 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001378452.1 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ITPR1 | NM_001378452.1 | c.7099G>A | p.Ala2367Thr | missense_variant | Exon 54 of 62 | ENST00000649015.2 | NP_001365381.1 | |
ITPR1 | NM_001168272.2 | c.7054G>A | p.Ala2352Thr | missense_variant | Exon 53 of 61 | NP_001161744.1 | ||
ITPR1 | NM_001099952.4 | c.6955G>A | p.Ala2319Thr | missense_variant | Exon 51 of 59 | NP_001093422.2 | ||
ITPR1 | NM_002222.7 | c.6910G>A | p.Ala2304Thr | 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.7099G>A | p.Ala2367Thr | missense_variant | Exon 54 of 62 | NM_001378452.1 | ENSP00000497605.1 | |||
ITPR1 | ENST00000354582.12 | c.7075G>A | p.Ala2359Thr | missense_variant | Exon 54 of 62 | 5 | ENSP00000346595.8 | |||
ITPR1 | ENST00000648266.1 | c.7072G>A | p.Ala2358Thr | missense_variant | Exon 54 of 62 | ENSP00000498014.1 | ||||
ITPR1 | ENST00000650294.1 | c.7057G>A | p.Ala2353Thr | missense_variant | Exon 53 of 61 | ENSP00000498056.1 | ||||
ITPR1 | ENST00000443694.5 | c.7054G>A | p.Ala2352Thr | missense_variant | Exon 53 of 61 | 1 | ENSP00000401671.2 | |||
ITPR1 | ENST00000648309.1 | c.7027G>A | p.Ala2343Thr | missense_variant | Exon 51 of 59 | ENSP00000497026.1 | ||||
ITPR1 | ENST00000357086.10 | c.6955G>A | p.Ala2319Thr | missense_variant | Exon 51 of 59 | 1 | ENSP00000349597.4 | |||
ITPR1 | ENST00000456211.8 | c.6910G>A | p.Ala2304Thr | missense_variant | Exon 50 of 58 | 1 | ENSP00000397885.2 | |||
ITPR1 | ENST00000648038.1 | c.4861G>A | p.Ala1621Thr | missense_variant | Exon 34 of 42 | ENSP00000497872.1 | ||||
ITPR1 | ENST00000648431.1 | c.4276G>A | p.Ala1426Thr | missense_variant | Exon 31 of 39 | ENSP00000498149.1 | ||||
ITPR1 | ENST00000648212.1 | c.4039G>A | p.Ala1347Thr | missense_variant | Exon 31 of 39 | ENSP00000498022.1 |
Frequencies
GnomAD3 genomes AF: 0.000677 AC: 103AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000823 AC: 205AN: 249024Hom.: 0 AF XY: 0.000829 AC XY: 112AN XY: 135098
GnomAD4 exome AF: 0.000786 AC: 1149AN: 1461498Hom.: 1 Cov.: 32 AF XY: 0.000781 AC XY: 568AN XY: 727050
GnomAD4 genome AF: 0.000677 AC: 103AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.000699 AC XY: 52AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:5Benign:1
- -
- -
ITPR1: PP3 -
Reported as maternally inherited variant in individual with autism spectrum disorder; however, additional clinical information was not provided and information regarding parental phenotype was not available (Guo et al., 2018); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32859249, 30564305, 29232918) -
- -
BS1 -
not specified Benign:1
- -
ITPR1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Autosomal dominant cerebellar ataxia Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at