chr7-105532344-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_021930.6(RINT1):c.29C>T(p.Ser10Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000262 in 1,600,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. S10Y) has been classified as Likely benign.
Frequency
Consequence
NM_021930.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RINT1 | NM_021930.6 | c.29C>T | p.Ser10Phe | missense_variant | 1/15 | ENST00000257700.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RINT1 | ENST00000257700.7 | c.29C>T | p.Ser10Phe | missense_variant | 1/15 | 1 | NM_021930.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152258Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000454 AC: 1AN: 220474Hom.: 0 AF XY: 0.00000825 AC XY: 1AN XY: 121266
GnomAD4 exome AF: 0.0000283 AC: 41AN: 1448036Hom.: 0 Cov.: 31 AF XY: 0.0000264 AC XY: 19AN XY: 719536
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152258Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74396
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2024 | The p.S10F variant (also known as c.29C>T), located in coding exon 1 of the RINT1 gene, results from a C to T substitution at nucleotide position 29. The serine at codon 10 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 03, 2021 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RINT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 645732). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with phenylalanine at codon 10 of the RINT1 protein (p.Ser10Phe). The serine residue is weakly conserved and there is a large physicochemical difference between serine and phenylalanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at