chr1-204155021-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_000537.4(REN):c.1216C>T(p.Arg406Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,613,912 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 (★★).
Frequency
Consequence
NM_000537.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
REN | ENST00000272190.9 | c.1216C>T | p.Arg406Cys | missense_variant | Exon 10 of 10 | 1 | NM_000537.4 | ENSP00000272190.8 | ||
REN | ENST00000638118.1 | c.1102C>T | p.Arg368Cys | missense_variant | Exon 12 of 12 | 5 | ENSP00000490307.1 |
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152268Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000842 AC: 21AN: 249546Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135010
GnomAD4 exome AF: 0.0000965 AC: 141AN: 1461526Hom.: 0 Cov.: 31 AF XY: 0.0000674 AC XY: 49AN XY: 727046
GnomAD4 genome AF: 0.000177 AC: 27AN: 152386Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15AN XY: 74530
ClinVar
Submissions by phenotype
Hepatoblastoma Pathogenic:1
- -
Familial juvenile hyperuricemic nephropathy type 2;C5681536:Renal tubular dysgenesis of genetic origin Uncertain:1
- -
not provided Uncertain:1
This variant has not been reported in the literature in individuals affected with REN-related conditions. This variant is present in population databases (rs547414447, gnomAD 0.03%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 406 of the REN protein (p.Arg406Cys). ClinVar contains an entry for this variant (Variation ID: 1343309). 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at