rs111586358

Variant names:

• chr11-3683214-C-A
• NM_016320.5:c.4904G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-3683214-C-A
• chr11-3683214-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016320.5(NUP98):​c.4904G>T​(p.Arg1635Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUP98 NM_016320.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.518

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29076788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP98	NM_016320.5	c.4904G>T	p.Arg1635Leu	missense_variant	Exon 30 of 33	ENST00000324932.12	NP_057404.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP98	ENST00000324932.12	c.4904G>T	p.Arg1635Leu	missense_variant	Exon 30 of 33	1	NM_016320.5	ENSP00000316032.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.40	.;T;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;M;.
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.3	D;.;D
REVEL	Benign	0.099
Sift	Uncertain	0.014	D;.;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.73	P;.;P
Vest4		0.57
MutPred		0.53		Loss of MoRF binding (P = 0.0172);.;.;
MVP		0.19
MPC		0.40
ClinPred		0.88	D
GERP RS		0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.077
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-3704444;