rs367592989
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001077350.3(NPRL3):c.447C>T(p.Ile149=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000283 in 1,612,226 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
NPRL3
NM_001077350.3 synonymous
NM_001077350.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.617
Genes affected
NPRL3 (HGNC:14124): (NPR3 like, GATOR1 complex subunit) Contributes to GTPase activator activity. Involved in cellular response to amino acid starvation and negative regulation of TOR signaling. Located in lysosomal membrane. Part of GATOR1 complex. Implicated in focal epilepsy. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 16-112722-G-A is Benign according to our data. Variant chr16-112722-G-A is described in ClinVar as [Benign]. Clinvar id is 476223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.617 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00143 (218/152340) while in subpopulation AFR AF= 0.00505 (210/41580). AF 95% confidence interval is 0.00449. There are 1 homozygotes in gnomad4. There are 102 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 218 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NPRL3 | NM_001077350.3 | c.447C>T | p.Ile149= | synonymous_variant | 6/14 | ENST00000611875.5 | NP_001070818.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NPRL3 | ENST00000611875.5 | c.447C>T | p.Ile149= | synonymous_variant | 6/14 | 5 | NM_001077350.3 | ENSP00000478273 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00143 AC: 218AN: 152222Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000333 AC: 82AN: 246124Hom.: 0 AF XY: 0.000247 AC XY: 33AN XY: 133770
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GnomAD4 exome AF: 0.000164 AC: 239AN: 1459886Hom.: 0 Cov.: 31 AF XY: 0.000132 AC XY: 96AN XY: 726024
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GnomAD4 genome AF: 0.00143 AC: 218AN: 152340Hom.: 1 Cov.: 33 AF XY: 0.00137 AC XY: 102AN XY: 74488
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 30, 2019 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Epilepsy, familial focal, with variable foci 3 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at