rs373694009
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001378452.1(ITPR1):c.2111G>A(p.Ser704Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,610,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S704T) has been classified as Likely benign.
Frequency
Consequence
NM_001378452.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITPR1 | NM_001378452.1 | c.2111G>A | p.Ser704Asn | missense_variant | 20/62 | ENST00000649015.2 | |
ITPR1 | NM_001168272.2 | c.2066G>A | p.Ser689Asn | missense_variant | 19/61 | ||
ITPR1 | NM_001099952.4 | c.2111G>A | p.Ser704Asn | missense_variant | 20/59 | ||
ITPR1 | NM_002222.7 | c.2066G>A | p.Ser689Asn | missense_variant | 19/58 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITPR1 | ENST00000649015.2 | c.2111G>A | p.Ser704Asn | missense_variant | 20/62 | NM_001378452.1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152190Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000205 AC: 5AN: 243632Hom.: 0 AF XY: 0.0000303 AC XY: 4AN XY: 132002
GnomAD4 exome AF: 0.0000199 AC: 29AN: 1458488Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 725126
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74476
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 18, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 04, 2022 | 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 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 08, 2022 | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 689 of the ITPR1 protein (p.Ser689Asn). 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. 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. ClinVar contains an entry for this variant (Variation ID: 586043). This variant has not been reported in the literature in individuals affected with ITPR1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at