chr3-4645604-A-C
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2PM5PP2PP3_StrongPP5_Moderate
The NM_001378452.1(ITPR1):c.731A>C(p.His244Pro) 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. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H244R) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001378452.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITPR1 | NM_001378452.1 | c.731A>C | p.His244Pro | missense_variant | 10/62 | ENST00000649015.2 | |
ITPR1 | NM_001168272.2 | c.731A>C | p.His244Pro | missense_variant | 10/61 | ||
ITPR1 | NM_001099952.4 | c.731A>C | p.His244Pro | missense_variant | 10/59 | ||
ITPR1 | NM_002222.7 | c.731A>C | p.His244Pro | missense_variant | 10/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITPR1 | ENST00000649015.2 | c.731A>C | p.His244Pro | missense_variant | 10/62 | NM_001378452.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2024 | The c.731A>C (p.H244P) alteration is located in exon 10 (coding exon 8) of the ITPR1 gene. This alteration results from an A to C substitution at nucleotide position 731, causing the histidine (H) at amino acid position 244 to be replaced by a proline (P)._x000D_ _x000D_ for ITPR1-related congenital non-progressive spinocerebellar ataxia (SCA29); however, its clinical significance for Gillespie syndrome is uncertain and it is unlikely to be causative of ITPR1-related spinocerebellar ataxia (SCA15). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at