3-4516493-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_SupportingPM2
The NM_001378452.1(ITPR1):āc.2T>Cā(p.Met1?) variant causes a start lost change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,407,762 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 (ā ).
Frequency
Consequence
NM_001378452.1 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ITPR1 | NM_001378452.1 | c.2T>C | p.Met1? | start_lost | Exon 3 of 62 | ENST00000649015.2 | NP_001365381.1 | |
ITPR1 | NM_001168272.2 | c.2T>C | p.Met1? | start_lost | Exon 3 of 61 | NP_001161744.1 | ||
ITPR1 | NM_001099952.4 | c.2T>C | p.Met1? | start_lost | Exon 3 of 59 | NP_001093422.2 | ||
ITPR1 | NM_002222.7 | c.2T>C | p.Met1? | start_lost | Exon 3 of 58 | NP_002213.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ITPR1 | ENST00000649015.2 | c.2T>C | p.Met1? | start_lost | Exon 3 of 62 | NM_001378452.1 | ENSP00000497605.1 | |||
ITPR1 | ENST00000354582.12 | c.2T>C | p.Met1? | start_lost | Exon 3 of 62 | 5 | ENSP00000346595.8 | |||
ITPR1 | ENST00000648266.1 | c.2T>C | p.Met1? | start_lost | Exon 3 of 62 | ENSP00000498014.1 | ||||
ITPR1 | ENST00000650294.1 | c.2T>C | p.Met1? | start_lost | Exon 3 of 61 | ENSP00000498056.1 | ||||
ITPR1 | ENST00000443694.5 | c.2T>C | p.Met1? | start_lost | Exon 3 of 61 | 1 | ENSP00000401671.2 | |||
ITPR1 | ENST00000648309.1 | c.2T>C | p.Met1? | start_lost | Exon 1 of 59 | ENSP00000497026.1 | ||||
ITPR1 | ENST00000357086.10 | c.2T>C | p.Met1? | start_lost | Exon 3 of 59 | 1 | ENSP00000349597.4 | |||
ITPR1 | ENST00000456211.8 | c.2T>C | p.Met1? | start_lost | Exon 3 of 58 | 1 | ENSP00000397885.2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000142 AC: 2AN: 1407762Hom.: 0 Cov.: 26 AF XY: 0.00000143 AC XY: 1AN XY: 700830
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
This variant has not been reported in the literature in individuals with ITPR1-related disease. However, this variant has been observed to be de novo in an individual affected with clinical features of spinocerebellar ataxia type 29 (SCA29) (Invitae). 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. This variant is expected to result in an absent or disrupted protein product. If translation initiation is rescued by the downstream methionine at codon 5, this would result in loss of first 4 amino acids from the N-terminal suppressor domain of the ITPR1 protein. This variant is not present in population databases (ExAC no frequency). This sequence change affects the initiator methionine of the ITPR1 mRNA. The next in-frame methionine is located at codon 5. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at