rs185684106
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BS1_Supporting
The NM_021930.6(RINT1):c.2032C>T(p.Leu678Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,614,114 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. L678P) has been classified as Uncertain significance.
Frequency
Consequence
NM_021930.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.2032C>T | p.Leu678Phe | missense_variant | 13/15 | ENST00000257700.7 | |
EFCAB10 | NM_001355526.2 | c.*25G>A | 3_prime_UTR_variant | 5/5 | ENST00000480514.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RINT1 | ENST00000257700.7 | c.2032C>T | p.Leu678Phe | missense_variant | 13/15 | 1 | NM_021930.6 | P1 | |
EFCAB10 | ENST00000480514.6 | c.*25G>A | 3_prime_UTR_variant | 5/5 | 1 | NM_001355526.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152132Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251378Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135860
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727232
GnomAD4 genome ? AF: 0.000131 AC: 20AN: 152250Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74438
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 05, 2023 | The p.L678F variant (also known as c.2032C>T), located in coding exon 13 of the RINT1 gene, results from a C to T substitution at nucleotide position 2032. The leucine at codon 678 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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 15, 2022 | 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 241402). This variant has not been reported in the literature in individuals affected with RINT1-related conditions. This variant is present in population databases (rs185684106, gnomAD 0.006%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 678 of the RINT1 protein (p.Leu678Phe). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at