rs758536777
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_021930.6(RINT1):c.61G>A(p.Asp21Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000929 in 1,614,038 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D21E) has been classified as Likely benign.
Frequency
Consequence
NM_021930.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RINT1 | NM_021930.6 | c.61G>A | p.Asp21Asn | missense_variant | 2/15 | ENST00000257700.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RINT1 | ENST00000257700.7 | c.61G>A | p.Asp21Asn | missense_variant | 2/15 | 1 | NM_021930.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251476Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135916
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461872Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727242
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74334
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 14, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 21 of the RINT1 protein (p.Asp21Asn). This variant is present in population databases (rs758536777, gnomAD 0.003%). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 410780). This variant has not been reported in the literature in individuals affected with RINT1-related conditions. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 01, 2022 | The p.D21N variant (also known as c.61G>A), located in coding exon 2 of the RINT1 gene, results from a G to A substitution at nucleotide position 61. The aspartic acid at codon 21 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at