rs1060503049
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_021930.6(RINT1):āc.1609T>Cā(p.Cys537Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C537S) has been classified as Uncertain significance.
Frequency
Consequence
NM_021930.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RINT1 | NM_021930.6 | c.1609T>C | p.Cys537Arg | missense_variant | 11/15 | ENST00000257700.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RINT1 | ENST00000257700.7 | c.1609T>C | p.Cys537Arg | missense_variant | 11/15 | 1 | NM_021930.6 | P1 | |
RINT1 | ENST00000474123.1 | n.613T>C | non_coding_transcript_exon_variant | 4/4 | 2 | ||||
RINT1 | ENST00000497979.5 | c.*1214T>C | 3_prime_UTR_variant, NMD_transcript_variant | 11/15 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152238Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461776Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727192
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74368
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 31, 2024 | The p.C537R variant (also known as c.1609T>C), located in coding exon 11 of the RINT1 gene, results from a T to C substitution at nucleotide position 1609. The cysteine at codon 537 is replaced by arginine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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 | Oct 30, 2019 | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a RINT1-related disease. This sequence change replaces cysteine with arginine at codon 537 of the RINT1 protein (p.Cys537Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at