NM_005124.4:c.4351G>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005124.4(NUP153):c.4351G>T(p.Gly1451Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000315 in 1,576,472 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00032 ( 1 hom. )

Consequence

NUP153
NM_005124.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.07

Variant links:

Genes affected

NUP153 (HGNC:8062): (nucleoporin 153) Nuclear pore complexes regulate the transport of macromolecules between the nucleus and cytoplasm. They are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. Nucleoporins are glycoproteins found in nuclear pores and contain characteristic pentapeptide XFXFG repeats as well as O-linked N-acetylglucosamine residues oriented towards the cytoplasm. The protein encoded by this gene has three distinct domains: a N-terminal region containing a pore targeting and an RNA-binding domain domain, a central region containing multiple zinc finger motifs, and a C-terminal region containing multiple XFXFG repeats. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, May 2013]

NUP153 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052980393).

BS2

High AC in GnomAd4 at 39 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP153	NM_005124.4 link	c.4351G>T	p.Gly1451Trp	missense_variant	Exon 22 of 22	ENST00000262077.3	NP_005115.2	P49790-1
NUP153	NM_001278209.2 link	c.4444G>T	p.Gly1482Trp	missense_variant	Exon 23 of 23		NP_001265138.1	P49790-3
NUP153	NM_001278210.2 link	c.4225G>T	p.Gly1409Trp	missense_variant	Exon 21 of 21		NP_001265139.1	P49790-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NUP153	ENST00000262077.3 link	c.4351G>T	p.Gly1451Trp	missense_variant	Exon 22 of 22	1	NM_005124.4	ENSP00000262077.3	P49790-1
NUP153	ENST00000613258.4 link	c.4225G>T	p.Gly1409Trp	missense_variant	Exon 21 of 21	1		ENSP00000478627.1	P49790-2
NUP153	ENST00000537253.5 link	c.4444G>T	p.Gly1482Trp	missense_variant	Exon 23 of 23	2		ENSP00000444029.1	P49790-3

Frequencies

GnomAD3 genomes

AF:

0.000268

AC:

AN:

145668

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00117

Gnomad ASJ

AF:

0.000875

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000108

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000268

Gnomad OTH

AF:

0.000502

GnomAD3 exomes

AF:

0.000303

AC:

AN:

251140

Hom.:

AF XY:

0.000273

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000326

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000319

AC:

457

AN:

1430694

Hom.:

Cov.:

AF XY:

0.000302

AC XY:

215

AN XY:

711272

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

Gnomad4 AMR exome

AF:

0.000229

Gnomad4 ASJ exome

AF:

0.00292

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000196

Gnomad4 NFE exome

AF:

0.000322

Gnomad4 OTH exome

AF:

0.000360

GnomAD4 genome

AF:

0.000268

AC:

AN:

145778

Hom.:

Cov.:

AF XY:

0.000355

AC XY:

AN XY:

70370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00117

Gnomad4 ASJ

AF:

0.000875

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000108

Gnomad4 NFE

AF:

0.000268

Gnomad4 OTH

AF:

0.000497

Alfa

AF:

0.000392

Hom.:

Bravo

AF:

0.000257

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4351G>T (p.G1451W) alteration is located in exon 22 (coding exon 22) of the NUP153 gene. This alteration results from a G to T substitution at nucleotide position 4351, causing the glycine (G) at amino acid position 1451 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.085

.;.;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.053

T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.4

.;.;M

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.8

.;D;D

REVEL

Benign

0.28

Sift

Pathogenic

0.0

.;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.58

MVP

0.49

MPC

0.26

ClinPred

0.69

GERP RS

4.8

Varity_R

0.59

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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