rs1186811814
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001034850.3(RETREG1):c.1418C>T(p.Thr473Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,686 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. T473R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001034850.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RETREG1 | NM_001034850.3 | c.1418C>T | p.Thr473Ile | missense_variant | 9/9 | ENST00000306320.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RETREG1 | ENST00000306320.10 | c.1418C>T | p.Thr473Ile | missense_variant | 9/9 | 1 | NM_001034850.3 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249166Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135182
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461686Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 727146
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 06, 2021 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with RETREG1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 473 of the RETREG1 protein (p.Thr473Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at