rs201898612
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_021930.6(RINT1):c.41C>T(p.Pro14Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,601,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P14P) has been classified as Uncertain significance.
Frequency
Consequence
NM_021930.6 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RINT1 | NM_021930.6 | c.41C>T | p.Pro14Leu | missense_variant, splice_region_variant | 1/15 | ENST00000257700.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RINT1 | ENST00000257700.7 | c.41C>T | p.Pro14Leu | missense_variant, splice_region_variant | 1/15 | 1 | NM_021930.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152264Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000996 AC: 22AN: 220830Hom.: 0 AF XY: 0.000107 AC XY: 13AN XY: 121344
GnomAD4 exome AF: 0.000198 AC: 287AN: 1449034Hom.: 0 Cov.: 31 AF XY: 0.000206 AC XY: 148AN XY: 720040
GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152264Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74394
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 | Nov 17, 2023 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 14 of the RINT1 protein (p.Pro14Leu). This variant is present in population databases (rs201898612, gnomAD 0.02%). This missense change has been observed in individual(s) with breast and/or ovarian cancer and melanoma (PMID: 27544226, 31567591). ClinVar contains an entry for this variant (Variation ID: 410798). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 26, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at