rs2228379

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005124.4(NUP153):c.4162A>G(p.Thr1388Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00366 in 1,612,918 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 97 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 101 hom. )

Consequence

NUP153
NM_005124.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.291

Publications

5 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011480153).

BP6

Variant 6-17624573-T-C is Benign according to our data. Variant chr6-17624573-T-C is described in ClinVar as Benign. ClinVar VariationId is 777401.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005124.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUP153	NM_005124.4	MANE Select	c.4162A>G	p.Thr1388Ala	missense	Exon 20 of 22	NP_005115.2
NUP153	NM_001278209.2		c.4255A>G	p.Thr1419Ala	missense	Exon 21 of 23	NP_001265138.1	P49790-3
NUP153	NM_001278210.2		c.4036A>G	p.Thr1346Ala	missense	Exon 19 of 21	NP_001265139.1	P49790-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUP153	ENST00000262077.3	TSL:1 MANE Select	c.4162A>G	p.Thr1388Ala	missense	Exon 20 of 22	ENSP00000262077.3	P49790-1
NUP153	ENST00000613258.4	TSL:1	c.4036A>G	p.Thr1346Ala	missense	Exon 19 of 21	ENSP00000478627.1	P49790-2
NUP153	ENST00000537253.5	TSL:2	c.4255A>G	p.Thr1419Ala	missense	Exon 21 of 23	ENSP00000444029.1	P49790-3

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2942

AN:

151262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0674

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00889

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:

0.000177

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.00524

AC:

1316

AN:

250932

AF XY:

0.00384

show subpopulations

Gnomad AFR exome

AF:

0.0715

Gnomad AMR exome

AF:

0.00391

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000618

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00203

AC:

2963

AN:

1461538

Hom.:

101

Cov.:

AF XY:

0.00179

AC XY:

1301

AN XY:

727042

show subpopulations

African (AFR)

AF:

0.0723

AC:

2421

AN:

33474

American (AMR)

AF:

0.00443

AC:

198

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000336

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000216

AC:

AN:

1111754

Other (OTH)

AF:

0.00467

AC:

282

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

145

291

436

582

727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0195

AC:

2948

AN:

151380

Hom.:

Cov.:

AF XY:

0.0181

AC XY:

1342

AN XY:

73950

show subpopulations

African (AFR)

AF:

0.0673

AC:

2772

AN:

41190

American (AMR)

AF:

0.00887

AC:

135

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10446

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000177

AC:

AN:

67844

Other (OTH)

AF:

0.0138

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

137

275

412

550

687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0148

Hom.:

Bravo

AF:

0.0223

ESP6500AA

AF:

0.0676

AC:

298

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00630

AC:

765

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.0041

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0011

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.2

PhyloP100

0.29

PrimateAI

Benign

0.33

PROVEAN

Benign

0.42

REVEL

Benign

0.075

Sift

Benign

1.0

Sift4G

Benign

0.89

Polyphen

0.0

Vest4

0.084

MVP

0.21

MPC

0.032

ClinPred

0.0020

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.020

gMVP

0.16

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over