rs2043635

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP93	NM_014669.5	c.298-13401A>G		intron_variant	Intron 3 of 21	ENST00000308159.10	NP_055484.3
NUP93	NM_001242795.2	c.-73+2861A>G		intron_variant	Intron 1 of 19		NP_001229724.1
NUP93	NM_001242796.2	c.-73+1203A>G		intron_variant	Intron 1 of 19		NP_001229725.1
NUP93	XM_005256263.4	c.298-13401A>G		intron_variant	Intron 3 of 21		XP_005256320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP93	ENST00000308159.10	c.298-13401A>G		intron_variant	Intron 3 of 21	1	NM_014669.5	ENSP00000310668.5

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

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.314

Alfa AF: 0.286 Hom.: 775

Bravo AF: 0.321

Asia WGS AF: 0.408 AC: 1418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2043635; hg19: chr16-56818987;