11-3741938-G-T

Variant names:

• chr11-3741938-G-T
• rs2672221
• NM_016320.5:c.1408+2571C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016320.5(NUP98):​c.1408+2571C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 152,264 control chromosomes in the GnomAD database, including 57,301 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 0.87 (57301 hom., cov: 32)
• Consequence: NUP98 NM_016320.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP98	NM_016320.5	c.1408+2571C>A		intron_variant	Intron 12 of 32	ENST00000324932.12	NP_057404.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP98	ENST00000324932.12	c.1408+2571C>A		intron_variant	Intron 12 of 32	1	NM_016320.5	ENSP00000316032.7

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131702 AN: 152146 Hom.: 57253 Cov.: 32

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.809

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.822

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.866 AC: 131807 AN: 152264 Hom.: 57301 Cov.: 32 AF XY: 0.870 AC XY: 64759 AN XY: 74450

African (AFR) AF: 0.956 AC: 39745 AN: 41562

American (AMR) AF: 0.827 AC: 12644 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.809 AC: 2807 AN: 3470

East Asian (EAS) AF: 0.965 AC: 5008 AN: 5192

South Asian (SAS) AF: 0.889 AC: 4288 AN: 4826

European-Finnish (FIN) AF: 0.882 AC: 9338 AN: 10592

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55341 AN: 68014

Other (OTH) AF: 0.819 AC: 1732 AN: 2114

Alfa AF: 0.829 Hom.: 146731

Bravo AF: 0.862

Asia WGS AF: 0.895 AC: 3113 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.34
DANN	Benign	0.32
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2672221; hg19: chr11-3763168;