Variant rs1875 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_016320.5(NUP98):c.4284G>A(p.Ala1428=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,613,184 control chromosomes in the GnomAD database, including 34,626 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4570 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30056 hom. )

Consequence

NUP98
NM_016320.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.469

Variant links:

Genes affected

NUP98 (HGNC:8068): (nucleoporin 98 and 96 precursor) Nuclear pore complexes (NPCs) regulate the transport of macromolecules between the nucleus and cytoplasm, and are composed of many polypeptide subunits, many of which belong to the nucleoporin family. This gene belongs to the nucleoporin gene family and encodes a 186 kDa precursor protein that undergoes autoproteolytic cleavage to generate a 98 kDa nucleoporin and 96 kDa nucleoporin. The 98 kDa nucleoporin contains a Gly-Leu-Phe-Gly (GLGF) repeat domain and participates in many cellular processes, including nuclear import, nuclear export, mitotic progression, and regulation of gene expression. The 96 kDa nucleoporin is a scaffold component of the NPC. Proteolytic cleavage is important for targeting of the proteins to the NPC. Translocations between this gene and many other partner genes have been observed in different leukemias. Rearrangements typically result in chimeras with the N-terminal GLGF domain of this gene to the C-terminus of the partner gene. Alternative splicing results in multiple transcript variants encoding different isoforms, at least two of which are proteolytically processed. Some variants lack the region that encodes the 96 kDa nucleoporin. [provided by RefSeq, Feb 2016]

NUP98 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP7

Synonymous conserved (PhyloP=-0.469 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP98	NM_016320.5 linkuse as main transcript	c.4284G>A	p.Ala1428=	synonymous_variant	27/33	ENST00000324932.12	NP_057404.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP98	ENST00000324932.12 linkuse as main transcript	c.4284G>A	p.Ala1428=	synonymous_variant	27/33	1	NM_016320.5	ENSP00000316032	P4	P52948-5

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34902

AN:

151904

Hom.:

4572

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.309

Gnomad SAS

AF:

0.296

Gnomad FIN

AF:

0.292

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.199

GnomAD3 exomes

AF:

0.205

AC:

51613

AN:

251394

Hom.:

6219

AF XY:

0.210

AC XY:

28598

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.0841

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.306

Gnomad SAS exome

AF:

0.298

Gnomad FIN exome

AF:

0.277

Gnomad NFE exome

AF:

0.176

Gnomad OTH exome

AF:

0.184

GnomAD4 exome

AF:

0.195

AC:

285427

AN:

1461160

Hom.:

30056

Cov.:

AF XY:

0.198

AC XY:

143924

AN XY:

726916

show subpopulations

Gnomad4 AFR exome

AF:

0.352

Gnomad4 AMR exome

AF:

0.0870

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.312

Gnomad4 SAS exome

AF:

0.296

Gnomad4 FIN exome

AF:

0.269

Gnomad4 NFE exome

AF:

0.181

Gnomad4 OTH exome

AF:

0.202

GnomAD4 genome

AF:

0.230

AC:

34935

AN:

152024

Hom.:

4570

Cov.:

AF XY:

0.233

AC XY:

17290

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.332

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.126

Gnomad4 EAS

AF:

0.309

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.292

Gnomad4 NFE

AF:

0.180

Gnomad4 OTH

AF:

0.203

Alfa

AF:

0.181

Hom.:

3363

Bravo

AF:

0.218

Asia WGS

AF:

0.290

AC:

1008

AN:

3478

EpiCase

AF:

0.176

EpiControl

AF:

0.169

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

8.7

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over