11-3700239-A-G

Variant names:

• chr11-3700239-A-G
• rs671572
• NM_016320.5:c.3742+371T>C

Variant summary

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

The NM_016320.5(NUP98):​c.3742+371T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 1.0 (72689 hom., cov: 19)
• Consequence: NUP98 NM_016320.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 1 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP98	NM_016320.5	MANE Select	c.3742+371T>C		intron	N/A	NP_057404.2
	NUP98	NM_001365125.2		c.3835+371T>C		intron	N/A	NP_001352054.1
	NUP98	NM_001365126.2		c.3793+371T>C		intron	N/A	NP_001352055.1	P52948-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP98	ENST00000324932.12	TSL:1 MANE Select	c.3742+371T>C		intron	N/A	ENSP00000316032.7	P52948-5
	NUP98	ENST00000429801.5	TSL:1	c.598+371T>C		intron	N/A	ENSP00000413146.1	H7C3P6
	NUP98	ENST00000915300.1		c.3886+371T>C		intron	N/A	ENSP00000585359.1

Frequencies

GnomAD3 genomes AF: 1.00 AC: 145304 AN: 145314 Hom.: 72647 Cov.: 19

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

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

GnomAD4 genome AF: 1.00 AC: 145388 AN: 145398 Hom.: 72689 Cov.: 19 AF XY: 1.00 AC XY: 70336 AN XY: 70338

African (AFR) AF: 1.00 AC: 38946 AN: 38950

American (AMR) AF: 1.00 AC: 14430 AN: 14430

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3452 AN: 3452

East Asian (EAS) AF: 1.00 AC: 4946 AN: 4946

South Asian (SAS) AF: 1.00 AC: 4474 AN: 4474

European-Finnish (FIN) AF: 1.00 AC: 8860 AN: 8860

Middle Eastern (MID) AF: 1.00 AC: 284 AN: 284

European-Non Finnish (NFE) AF: 1.00 AC: 67096 AN: 67102

Other (OTH) AF: 1.00 AC: 1998 AN: 1998

Alfa AF: 1.00 Hom.: 9249

Bravo AF: 1.00

Asia WGS AF: 0.999 AC: 3475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.50
DANN	Benign	0.27
PhyloP100		-1.5
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: rs671572; hg19: chr11-3721469;