chr20-19974948-C-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_018993.4(RIN2):c.923C>G(p.Pro308Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000455 in 1,603,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P308A) has been classified as Uncertain significance.
Frequency
Consequence
NM_018993.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RIN2 | NM_018993.4 | c.923C>G | p.Pro308Arg | missense_variant | 9/13 | ENST00000255006.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RIN2 | ENST00000255006.12 | c.923C>G | p.Pro308Arg | missense_variant | 9/13 | 2 | NM_018993.4 | P1 | |
RIN2 | ENST00000440354.2 | c.463+14137C>G | intron_variant | 1 | |||||
RIN2 | ENST00000484638.1 | n.767C>G | non_coding_transcript_exon_variant | 5/9 | 1 | ||||
RIN2 | ENST00000648440.1 | c.923C>G | p.Pro308Arg | missense_variant | 8/12 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000793 AC: 12AN: 151372Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000142 AC: 35AN: 247140Hom.: 0 AF XY: 0.000112 AC XY: 15AN XY: 134472
GnomAD4 exome AF: 0.0000420 AC: 61AN: 1452176Hom.: 0 Cov.: 51 AF XY: 0.0000360 AC XY: 26AN XY: 722778
GnomAD4 genome ? AF: 0.0000792 AC: 12AN: 151488Hom.: 0 Cov.: 32 AF XY: 0.0000810 AC XY: 6AN XY: 74116
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 21, 2022 | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 308 of the RIN2 protein (p.Pro308Arg). 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. This variant has not been reported in the literature in individuals affected with RIN2-related conditions. 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: "Not Available"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at