16-88794-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_001077350.3(NPRL3):c.1448C>T(p.Thr483Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,456 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T483T) has been classified as Likely benign.
Frequency
Consequence
NM_001077350.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPRL3 | NM_001077350.3 | c.1448C>T | p.Thr483Met | missense_variant | 13/14 | ENST00000611875.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPRL3 | ENST00000611875.5 | c.1448C>T | p.Thr483Met | missense_variant | 13/14 | 5 | NM_001077350.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152174Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247380Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134598
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461282Hom.: 1 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 726892
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152174Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74352
ClinVar
Submissions by phenotype
Epilepsy, familial focal, with variable foci 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2023 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 483 of the NPRL3 protein (p.Thr483Met). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NPRL3 protein function. ClinVar contains an entry for this variant (Variation ID: 580875). This variant has not been reported in the literature in individuals affected with NPRL3-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.004%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at