chr1-204155053-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_000537.4(REN):c.1184G>A(p.Arg395Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,836 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R395W) has been classified as Uncertain significance.
Frequency
Consequence
NM_000537.4 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 |
---|---|---|---|---|---|---|---|
REN | NM_000537.4 | c.1184G>A | p.Arg395Gln | missense_variant | 10/10 | ENST00000272190.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
REN | ENST00000272190.9 | c.1184G>A | p.Arg395Gln | missense_variant | 10/10 | 1 | NM_000537.4 | P1 | |
REN | ENST00000638118.1 | c.1070G>A | p.Arg357Gln | missense_variant | 12/12 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461836Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727214
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Familial juvenile hyperuricemic nephropathy type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen | Oct 10, 2023 | The detected change is not reported in the general population (gnomAD) (as of October 10, 2023). It has not yet been described in the ClinVar database or in the literature. From a bioinformatic perspective, the change is inconsistently classified as disease-causing (CADDphred 28.4, PolyPhen2), but also as “tolerated” and “benign” (SIFT, MutationTaster). The variant is currently considered a “variant of uncertain clinical significance” (ACMG criteria). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at