rs556232826
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_001077350.3(NPRL3):c.641C>T(p.Ser214Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,581,206 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 (★). Synonymous variant affecting the same amino acid position (i.e. S214S) 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPRL3 | NM_001077350.3 | c.641C>T | p.Ser214Leu | missense_variant | 8/14 | ENST00000611875.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPRL3 | ENST00000611875.5 | c.641C>T | p.Ser214Leu | missense_variant | 8/14 | 5 | NM_001077350.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000463 AC: 7AN: 151160Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000753 AC: 16AN: 212428Hom.: 0 AF XY: 0.0000520 AC XY: 6AN XY: 115484
GnomAD4 exome AF: 0.0000266 AC: 38AN: 1429928Hom.: 0 Cov.: 30 AF XY: 0.0000169 AC XY: 12AN XY: 710382
GnomAD4 genome ? AF: 0.0000463 AC: 7AN: 151278Hom.: 0 Cov.: 30 AF XY: 0.0000812 AC XY: 6AN XY: 73878
ClinVar
Submissions by phenotype
Epilepsy, familial focal, with variable foci 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 28, 2022 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 214 of the NPRL3 protein (p.Ser214Leu). This variant is present in population databases (rs556232826, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with NPRL3-related conditions. ClinVar contains an entry for this variant (Variation ID: 476227). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at