rs2043635

Variant names:

• chr16-56785075-A-G
• rs2043635
• NM_014669.5:c.298-13401A>G

Variant summary

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

The NM_014669.5(NUP93):​c.298-13401A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,108 control chromosomes in the GnomAD database, including 7,675 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 0.31 (7675 hom., cov: 32)
• Consequence: NUP93 NM_014669.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247
• Publications: 3 publications found

Genes affected

NUP93 (HGNC:28958): (nucleoporin 93) The nuclear pore complex is a massive structure that extends across the nuclear envelope, forming a gateway that regulates the flow of macromolecules between the nucleus and the cytoplasm. Nucleoporins are the main components of the nuclear pore complex in eukaryotic cells. This gene encodes a nucleoporin protein that localizes both to the basket of the pore and to the nuclear entry of the central gated channel of the pore. The encoded protein is a target of caspase cysteine proteases that play a central role in programmed cell death by apoptosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2016]

NUP93 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 12

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014669.5. 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
	NUP93	NM_014669.5	MANE Select	c.298-13401A>G		intron	N/A	NP_055484.3
	NUP93	NM_001242795.2		c.-73+2861A>G		intron	N/A	NP_001229724.1	Q8N1F7-2
	NUP93	NM_001242796.2		c.-73+1203A>G		intron	N/A	NP_001229725.1	Q8N1F7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP93	ENST00000308159.10	TSL:1 MANE Select	c.298-13401A>G		intron	N/A	ENSP00000310668.5	Q8N1F7-1
	NUP93	ENST00000569842.5	TSL:5	c.298-13401A>G		intron	N/A	ENSP00000458101.1	H3BVG0
	NUP93	ENST00000923937.1		c.298-13401A>G		intron	N/A	ENSP00000593996.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47161 AN: 151990 Hom.: 7673 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.310 AC: 47190 AN: 152108 Hom.: 7675 Cov.: 32 AF XY: 0.311 AC XY: 23136 AN XY: 74374

African (AFR) AF: 0.383 AC: 15877 AN: 41490

American (AMR) AF: 0.308 AC: 4714 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3472

East Asian (EAS) AF: 0.463 AC: 2393 AN: 5166

South Asian (SAS) AF: 0.366 AC: 1763 AN: 4818

European-Finnish (FIN) AF: 0.225 AC: 2377 AN: 10580

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18467 AN: 67976

Other (OTH) AF: 0.314 AC: 664 AN: 2112

Alfa AF: 0.289 Hom.: 828

Bravo AF: 0.321

Asia WGS AF: 0.408 AC: 1418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.55
PhyloP100		0.25
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2043635;

hg19: chr16-56818987;