rs8044753

Positions:

• chr16-56849526-G-A
• chr16-56849526-G-C
• chr16-56849526-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014669.5(NUP93):​c.*4917G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,140 control chromosomes in the GnomAD database, including 26,956 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 0.59 (26951 hom., cov: 32)
  • Exomes 𝑓: 0.61 (5 hom.)
• Consequence: NUP93 NM_014669.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.443

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP93	NM_014669.5	c.*4917G>A		3_prime_UTR_variant	22/22	ENST00000308159.10	NP_055484.3
NUP93	NM_001242795.2	c.*4917G>A		3_prime_UTR_variant	20/20		NP_001229724.1
NUP93	XM_005256263.4	c.*4917G>A		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.*4917G>A		3_prime_UTR_variant	22/22	1	NM_014669.5	ENSP00000310668.5
NUP93	ENST00000542526.5	c.*4917G>A		3_prime_UTR_variant	20/20	2		ENSP00000440235.1

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89229 AN: 151984 Hom.: 26923 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.650

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.611 AC: 22 AN: 36 Hom.: 5 Cov.: 0 AF XY: 0.618 AC XY: 21 AN XY: 34

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.615

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.587 AC: 89310 AN: 152104 Hom.: 26951 Cov.: 32 AF XY: 0.588 AC XY: 43713 AN XY: 74342

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.585

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.841

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.592

Alfa AF: 0.553 Hom.: 3249

Bravo AF: 0.604

Asia WGS AF: 0.741 AC: 2576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.70
DANN	Benign	0.22

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8044753; hg19: chr16-56883438;