rs572375358
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001077350.3(NPRL3):c.1107C>T(p.Ser369=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 1,613,844 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 0 hom. )
Consequence
NPRL3
NM_001077350.3 synonymous
NM_001077350.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.147
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
Variant 16-92650-G-A is Benign according to our data. Variant chr16-92650-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 476215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.147 with no splicing effect.
BS2
?
High AC in GnomAd4 at 29 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPRL3 | NM_001077350.3 | c.1107C>T | p.Ser369= | synonymous_variant | 11/14 | ENST00000611875.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPRL3 | ENST00000611875.5 | c.1107C>T | p.Ser369= | synonymous_variant | 11/14 | 5 | NM_001077350.3 | P1 | |
NPRL3 | ENST00000399953.7 | c.1032C>T | p.Ser344= | synonymous_variant | 9/12 | 1 | |||
NPRL3 | ENST00000621703.4 | c.*692C>T | 3_prime_UTR_variant, NMD_transcript_variant | 8/11 | 1 | ||||
NPRL3 | ENST00000622194.4 | c.*743C>T | 3_prime_UTR_variant, NMD_transcript_variant | 9/12 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000191 AC: 29AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000189 AC: 47AN: 248590Hom.: 0 AF XY: 0.000178 AC XY: 24AN XY: 134978
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GnomAD4 exome AF: 0.000227 AC: 332AN: 1461542Hom.: 0 Cov.: 31 AF XY: 0.000206 AC XY: 150AN XY: 727038
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GnomAD4 genome ? AF: 0.000190 AC: 29AN: 152302Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74474
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | NPRL3: BP4, BP7 - |
Epilepsy, familial focal, with variable foci 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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