1-229442058-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_018230.3(NUP133):​c.3335-18T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000355 in 1,542,940 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00038 ( 7 hom. )

Consequence

NUP133
NM_018230.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.07
Variant links:
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 -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 1-229442058-A-C is Benign according to our data. Variant chr1-229442058-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1990886.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000164 (25/152382) while in subpopulation EAS AF= 0.00481 (25/5196). AF 95% confidence interval is 0.00335. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NUP133NM_018230.3 linkuse as main transcriptc.3335-18T>G intron_variant ENST00000261396.6 NP_060700.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NUP133ENST00000261396.6 linkuse as main transcriptc.3335-18T>G intron_variant 1 NM_018230.3 ENSP00000261396 P1
NUP133ENST00000490352.1 linkuse as main transcriptn.382-18T>G intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.000164
AC:
25
AN:
152264
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00480
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000114
AC:
21
AN:
184648
Hom.:
0
AF XY:
0.000127
AC XY:
13
AN XY:
102160
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00180
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000376
AC:
523
AN:
1390558
Hom.:
7
Cov.:
29
AF XY:
0.000382
AC XY:
264
AN XY:
690374
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0148
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000696
GnomAD4 genome
AF:
0.000164
AC:
25
AN:
152382
Hom.:
0
Cov.:
32
AF XY:
0.000242
AC XY:
18
AN XY:
74516
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00481
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 30, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.25
DANN
Benign
0.48

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs142640601; hg19: chr1-229577805; COSMIC: COSV54571749; COSMIC: COSV54571749; API