1-229441955-G-A

Position:

chr1-229441955-G-A

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.444

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 -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 linkuse as main transcript	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 linkuse as main transcript	c.3420C>T	p.Phe1140=	synonymous_variant	26/26	1	NM_018230.3	ENSP00000261396	P1
NUP133	ENST00000490352.1 linkuse as main transcript	n.467C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000210

AC:

AN:

223406

Hom.:

AF XY:

0.000214

AC XY:

AN XY:

121524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000756

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000244

Gnomad OTH exome

AF:

0.000373

GnomAD4 exome

AF:

0.000263

AC:

376

AN:

1432216

Hom.:

Cov.:

AF XY:

0.000251

AC XY:

179

AN XY:

712052

show subpopulations

Gnomad4 AFR exome

AF:

0.0000318

Gnomad4 AMR exome

AF:

0.00141

Gnomad4 ASJ exome

AF:

0.0000396

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000274

Gnomad4 OTH exome

AF:

0.000337

GnomAD4 genome

AF:

0.000250

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000335

Hom.:

Bravo

AF:

0.000325

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

7.5

DANN

Benign

0.81

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