rs735144

Positions:

• chr16-56850012-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NUP93	NM_014669.5	c.*5403A>G		3_prime_UTR_variant	22/22	ENST00000308159.10	NP_055484.3
NUP93	NM_001242795.2	c.*5403A>G		3_prime_UTR_variant	20/20		NP_001229724.1
NUP93	XM_005256263.4	c.*5403A>G		3_prime_UTR_variant	22/22		XP_005256320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP93	ENST00000308159.10	c.*5403A>G		3_prime_UTR_variant	22/22	1	NM_014669.5	ENSP00000310668.5
NUP93	ENST00000542526.5	c.*5403A>G		3_prime_UTR_variant	20/20	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

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 1.00

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

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.441

Alfa AF: 0.425 Hom.: 9599

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs735144; hg19: chr16-56883924;