rs1453118437
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_001077350.3(NPRL3):c.1589T>C(p.Met530Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,130 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. M530I) has been classified as Uncertain significance.
Frequency
Consequence
NM_001077350.3 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 |
---|---|---|---|---|---|---|---|
NPRL3 | NM_001077350.3 | c.1589T>C | p.Met530Thr | missense_variant | 14/14 | ENST00000611875.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPRL3 | ENST00000611875.5 | c.1589T>C | p.Met530Thr | missense_variant | 14/14 | 5 | NM_001077350.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 exomes AF: 0.00000405 AC: 1AN: 246806Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134334
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461130Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 726794
GnomAD4 genome ? Cov.: 34
ClinVar
Submissions by phenotype
Epilepsy, familial focal, with variable foci 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 20, 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: "Tolerated"; PolyPhen-2: "Possibly 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 an NPRL3-related disease. This sequence change replaces methionine with threonine at codon 530 of the NPRL3 protein (p.Met530Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at