rs201804963
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6
The NM_001378452.1(ITPR1):c.1034G>A(p.Arg345Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,613,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R345W) has been classified as Uncertain significance.
Frequency
Consequence
NM_001378452.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITPR1 | NM_001378452.1 | c.1034G>A | p.Arg345Gln | missense_variant | 13/62 | ENST00000649015.2 | |
ITPR1 | NM_001168272.2 | c.989G>A | p.Arg330Gln | missense_variant | 12/61 | ||
ITPR1 | NM_001099952.4 | c.1034G>A | p.Arg345Gln | missense_variant | 13/59 | ||
ITPR1 | NM_002222.7 | c.989G>A | p.Arg330Gln | missense_variant | 12/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITPR1 | ENST00000649015.2 | c.1034G>A | p.Arg345Gln | missense_variant | 13/62 | NM_001378452.1 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152100Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000165 AC: 41AN: 248808Hom.: 0 AF XY: 0.000163 AC XY: 22AN XY: 134984
GnomAD4 exome AF: 0.0000890 AC: 130AN: 1460976Hom.: 0 Cov.: 31 AF XY: 0.0000977 AC XY: 71AN XY: 726758
GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152100Hom.: 0 Cov.: 31 AF XY: 0.000162 AC XY: 12AN XY: 74260
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 25, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 03, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 01, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533) - |
Autosomal dominant cerebellar ataxia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at