chr1-229487591-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018230.3(NUP133):c.1217A>G(p.Gln406Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,608,564 control chromosomes in the GnomAD database, including 45,710 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q406W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.30 ( 8793 hom., cov: 32)

Exomes 𝑓: 0.22 ( 36917 hom. )

Consequence

NUP133
NM_018230.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.80

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]

NUP133 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.0435452E-4).

BP6

Variant 1-229487591-T-C is Benign according to our data. Variant chr1-229487591-T-C is described in ClinVar as [Benign]. Clinvar id is 1601070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP133	NM_018230.3 link	c.1217A>G	p.Gln406Arg	missense_variant	Exon 10 of 26	ENST00000261396.6	NP_060700.2	Q8WUM0
NUP133	XM_047424979.1 link	c.1217A>G	p.Gln406Arg	missense_variant	Exon 10 of 19		XP_047280935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP133	ENST00000261396.6 link	c.1217A>G	p.Gln406Arg	missense_variant	Exon 10 of 26	1	NM_018230.3	ENSP00000261396.3		Q8WUM0

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45942

AN:

151930

Hom.:

8761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.538

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.385

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.319

GnomAD3 exomes

AF:

0.231

AC:

57236

AN:

247280

Hom.:

7750

AF XY:

0.225

AC XY:

30055

AN XY:

133662

show subpopulations

Gnomad AFR exome

AF:

0.537

Gnomad AMR exome

AF:

0.250

Gnomad ASJ exome

AF:

0.386

Gnomad EAS exome

AF:

0.170

Gnomad SAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.216

AC:

314085

AN:

1456516

Hom.:

36917

Cov.:

AF XY:

0.214

AC XY:

155150

AN XY:

724548

show subpopulations

Gnomad4 AFR exome

AF:

0.550

Gnomad4 AMR exome

AF:

0.258

Gnomad4 ASJ exome

AF:

0.379

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.188

Gnomad4 FIN exome

AF:

0.130

Gnomad4 NFE exome

AF:

0.207

Gnomad4 OTH exome

AF:

0.242

GnomAD4 genome

AF:

0.303

AC:

46021

AN:

152048

Hom.:

8793

Cov.:

AF XY:

0.296

AC XY:

22028

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.538

Gnomad4 AMR

AF:

0.290

Gnomad4 ASJ

AF:

0.385

Gnomad4 EAS

AF:

0.156

Gnomad4 SAS

AF:

0.171

Gnomad4 FIN

AF:

0.127

Gnomad4 NFE

AF:

0.206

Gnomad4 OTH

AF:

0.318

Alfa

AF:

0.219

Hom.:

7389

Bravo

AF:

0.328

TwinsUK

AF:

0.205

AC:

759

ALSPAC

AF:

0.207

AC:

798

ESP6500AA

AF:

0.527

AC:

2321

ESP6500EA

AF:

0.217

AC:

1863

ExAC

AF:

0.233

AC:

28313

Asia WGS

AF:

0.205

AC:

712

AN:

3478

EpiCase

AF:

0.222

EpiControl

AF:

0.224

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.5

DANN

Benign

0.14

DEOGEN2

Benign

0.10

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.26

MetaRNN

Benign

0.00020

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-2.2

PrimateAI

Benign

0.24

PROVEAN

Benign

1.1

REVEL

Benign

0.081

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.0040

MPC

0.16

ClinPred

0.00080

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.045

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over