chr11-3701074-T-C

Variant names:

• chr11-3701074-T-C
• rs685782
• NM_016320.5:c.3513-235A>G

Variant summary

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

The NM_016320.5(NUP98):​c.3513-235A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,036 control chromosomes in the GnomAD database, including 2,838 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 0.19 (2838 hom., cov: 32)
• Consequence: NUP98 NM_016320.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016320.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP98	NM_016320.5	MANE Select	c.3513-235A>G		intron	N/A	NP_057404.2
	NUP98	NM_001365125.2		c.3606-235A>G		intron	N/A	NP_001352054.1
	NUP98	NM_001365126.2		c.3564-235A>G		intron	N/A	NP_001352055.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP98	ENST00000324932.12	TSL:1 MANE Select	c.3513-235A>G		intron	N/A	ENSP00000316032.7
	NUP98	ENST00000429801.5	TSL:1	c.369-235A>G		intron	N/A	ENSP00000413146.1
	NUP98	ENST00000359171.8	TSL:5	c.3564-235A>G		intron	N/A	ENSP00000352091.5

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28567 AN: 151918 Hom.: 2838 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.0994

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.188 AC: 28582 AN: 152036 Hom.: 2838 Cov.: 32 AF XY: 0.190 AC XY: 14138 AN XY: 74334

African (AFR) AF: 0.191 AC: 7932 AN: 41460

American (AMR) AF: 0.0992 AC: 1514 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3470

East Asian (EAS) AF: 0.257 AC: 1333 AN: 5178

South Asian (SAS) AF: 0.179 AC: 862 AN: 4816

European-Finnish (FIN) AF: 0.289 AC: 3053 AN: 10556

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12983 AN: 67974

Other (OTH) AF: 0.171 AC: 360 AN: 2108

Alfa AF: 0.183 Hom.: 11483

Bravo AF: 0.173

Asia WGS AF: 0.204 AC: 706 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		-0.23
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: rs685782; hg19: chr11-3722304;