7-105565368-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_021930.6(RINT1):c.1978C>T(p.Leu660Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L660I) has been classified as Benign.
Frequency
Consequence
NM_021930.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RINT1 | NM_021930.6 | c.1978C>T | p.Leu660Phe | missense_variant | 13/15 | ENST00000257700.7 | |
EFCAB10 | NM_001355526.2 | c.*79G>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.1978C>T | p.Leu660Phe | missense_variant | 13/15 | 1 | NM_021930.6 | P1 | |
EFCAB10 | ENST00000480514.6 | c.*79G>A | 3_prime_UTR_variant | 5/5 | 1 | NM_001355526.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251436Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135888
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461848Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727228
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 06, 2024 | The p.L660F variant (also known as c.1978C>T), located in coding exon 13 of the RINT1 gene, results from a C to T substitution at nucleotide position 1978. The leucine at codon 660 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 07, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 660 of the RINT1 protein (p.Leu660Phe). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 836753). This variant has not been reported in the literature in individuals affected with RINT1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at