16-56801800-G-T

Variant names:

• chr16-56801800-G-T
• rs8051691
• NM_014669.5:c.360+3262G>T

Variant summary

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

The NM_014669.5(NUP93):​c.360+3262G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 152,022 control chromosomes in the GnomAD database, including 8,455 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 0.32 (8455 hom., cov: 32)
• Consequence: NUP93 NM_014669.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555
• Publications: 8 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: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP93	NM_014669.5	MANE Select	c.360+3262G>T		intron	N/A	NP_055484.3
	NUP93	NM_001242795.2		c.-10+3262G>T		intron	N/A	NP_001229724.1
	NUP93	NM_001242796.2		c.-10+3262G>T		intron	N/A	NP_001229725.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP93	ENST00000308159.10	TSL:1 MANE Select	c.360+3262G>T		intron	N/A	ENSP00000310668.5
	NUP93	ENST00000569842.5	TSL:5	c.360+3262G>T		intron	N/A	ENSP00000458101.1
	NUP93	ENST00000542526.5	TSL:2	c.-10+3262G>T		intron	N/A	ENSP00000440235.1

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49114 AN: 151904 Hom.: 8448 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.323 AC: 49161 AN: 152022 Hom.: 8455 Cov.: 32 AF XY: 0.324 AC XY: 24088 AN XY: 74312

African (AFR) AF: 0.427 AC: 17705 AN: 41442

American (AMR) AF: 0.315 AC: 4817 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 751 AN: 3470

East Asian (EAS) AF: 0.462 AC: 2391 AN: 5174

South Asian (SAS) AF: 0.366 AC: 1762 AN: 4812

European-Finnish (FIN) AF: 0.225 AC: 2382 AN: 10564

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

European-Non Finnish (NFE) AF: 0.272 AC: 18473 AN: 67954

Other (OTH) AF: 0.325 AC: 685 AN: 2110

Alfa AF: 0.258 Hom.: 2706

Bravo AF: 0.336

Asia WGS AF: 0.410 AC: 1426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.69
DANN	Benign	0.53
PhyloP100		-0.56
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: rs8051691; hg19: chr16-56835712;