chr20-19974948-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_018993.4(RIN2):c.923C>T(p.Pro308Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000567 in 1,603,548 control chromosomes in the GnomAD database, including 1 homozygotes. 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
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RIN2 | NM_018993.4 | c.923C>T | p.Pro308Leu | missense_variant | 9/13 | ENST00000255006.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RIN2 | ENST00000255006.12 | c.923C>T | p.Pro308Leu | missense_variant | 9/13 | 2 | NM_018993.4 | P1 | |
RIN2 | ENST00000440354.2 | c.463+14137C>T | intron_variant | 1 | |||||
RIN2 | ENST00000484638.1 | n.767C>T | non_coding_transcript_exon_variant | 5/9 | 1 | ||||
RIN2 | ENST00000648440.1 | c.923C>T | p.Pro308Leu | missense_variant | 8/12 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000793 AC: 12AN: 151372Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000125 AC: 31AN: 247140Hom.: 0 AF XY: 0.000141 AC XY: 19AN XY: 134472
GnomAD4 exome AF: 0.0000544 AC: 79AN: 1452176Hom.: 1 Cov.: 51 AF XY: 0.0000512 AC XY: 37AN XY: 722778
GnomAD4 genome AF: 0.0000793 AC: 12AN: 151372Hom.: 0 Cov.: 32 AF XY: 0.0000811 AC XY: 6AN XY: 73990
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2023 | The c.923C>T (p.P308L) alteration is located in exon 7 (coding exon 7) of the RIN2 gene. This alteration results from a C to T substitution at nucleotide position 923, causing the proline (P) at amino acid position 308 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 18, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at