rs735144

Variant names:

• chr16-56850012-A-G
• rs735144
• NM_014669.5:c.*5403A>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.*5403A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,116 control chromosomes in the GnomAD database, including 13,697 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 0.42 (13696 hom., cov: 33)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: NUP93 NM_014669.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.694
• Publications: 6 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 = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP93	NM_014669.5	c.*5403A>G		3_prime_UTR_variant	Exon 22 of 22	ENST00000308159.10	NP_055484.3
NUP93	NM_001242795.2	c.*5403A>G		3_prime_UTR_variant	Exon 20 of 20		NP_001229724.1
NUP93	XM_005256263.4	c.*5403A>G		3_prime_UTR_variant	Exon 22 of 22		XP_005256320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP93	ENST00000308159.10	c.*5403A>G		3_prime_UTR_variant	Exon 22 of 22	1	NM_014669.5	ENSP00000310668.5
NUP93	ENST00000542526.5	c.*5403A>G		3_prime_UTR_variant	Exon 20 of 20	2		ENSP00000440235.1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64078 AN: 151992 Hom.: 13704 Cov.: 33

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.441

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.421 AC: 64094 AN: 152112 Hom.: 13696 Cov.: 33 AF XY: 0.423 AC XY: 31432 AN XY: 74358

African (AFR) AF: 0.416 AC: 17265 AN: 41486

American (AMR) AF: 0.414 AC: 6333 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1435 AN: 3470

East Asian (EAS) AF: 0.615 AC: 3185 AN: 5176

South Asian (SAS) AF: 0.524 AC: 2526 AN: 4822

European-Finnish (FIN) AF: 0.327 AC: 3461 AN: 10582

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.419 AC: 28504 AN: 67978

Other (OTH) AF: 0.441 AC: 932 AN: 2112

Alfa AF: 0.427 Hom.: 13863

Bravo AF: 0.428

Asia WGS AF: 0.528 AC: 1834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.68
PhyloP100		-0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs735144; hg19: chr16-56883924;