chr1-229441955-G-A
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 2P and 15B. PM2BP4_ModerateBP6_Very_StrongBP7BS1
The NM_018230.3(NUP133):c.3420C>T(p.Phe1140=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 1,584,508 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 0.00025 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00026 ( 0 hom. )
Consequence
NUP133
NM_018230.3 synonymous
NM_018230.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.444
Genes affected
NUP133 (HGNC:18016): (nucleoporin 133) The nuclear envelope creates distinct nuclear and cytoplasmic compartments in eukaryotic cells. It consists of two concentric membranes perforated by nuclear pores, large protein complexes that form aqueous channels to regulate the flow of macromolecules between the nucleus and the cytoplasm. These complexes are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. The nucleoporin protein encoded by this gene displays evolutionarily conserved interactions with other nucleoporins. This protein, which localizes to both sides of the nuclear pore complex at interphase, remains associated with the complex during mitosis and is targeted at early stages to the reforming nuclear envelope. This protein also localizes to kinetochores of mitotic cells. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
Variant 1-229441955-G-A is Benign according to our data. Variant chr1-229441955-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2640062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.444 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00025 (38/152292) while in subpopulation AMR AF= 0.00105 (16/15300). AF 95% confidence interval is 0.000656. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| NUP133 | NM_018230.3 | c.3420C>T | p.Phe1140= | synonymous_variant | 26/26 | ENST00000261396.6 | NP_060700.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| NUP133 | ENST00000261396.6 | c.3420C>T | p.Phe1140= | synonymous_variant | 26/26 | 1 | NM_018230.3 | ENSP00000261396 | P1 | |
| NUP133 | ENST00000490352.1 | n.467C>T | non_coding_transcript_exon_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes 0.000250 AC: 38AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000210 AC: 47AN: 223406Hom.: 0 AF XY: 0.000214 AC XY: 26AN XY: 121524
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GnomAD4 exome AF: 0.000263 AC: 376AN: 1432216Hom.: 0 Cov.: 30 AF XY: 0.000251 AC XY: 179AN XY: 712052
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GnomAD4 genome 0.000250 AC: 38AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74454
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
| Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | NUP133: BP4, BP7 - |
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 20, 2023 | - - |
NUP133-related disorder Benign:1
| Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 29, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at