16-56785259-T-G

Variant names:

• chr16-56785259-T-G
• rs6416772
• NM_014669.5:c.298-13217T>G

Variant summary

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

The NM_014669.5(NUP93):​c.298-13217T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,030 control chromosomes in the GnomAD database, including 45,065 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 0.77 (45065 hom., cov: 30)
• Consequence: NUP93 NM_014669.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP93	NM_014669.5	c.298-13217T>G		intron_variant	Intron 3 of 21	ENST00000308159.10	NP_055484.3
NUP93	NM_001242795.2	c.-73+3045T>G		intron_variant	Intron 1 of 19		NP_001229724.1
NUP93	NM_001242796.2	c.-73+1387T>G		intron_variant	Intron 1 of 19		NP_001229725.1
NUP93	XM_005256263.4	c.298-13217T>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.298-13217T>G		intron_variant	Intron 3 of 21	1	NM_014669.5	ENSP00000310668.5

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116539 AN: 151912 Hom.: 44996 Cov.: 30

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.952

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.767 AC: 116669 AN: 152030 Hom.: 45065 Cov.: 30 AF XY: 0.768 AC XY: 57061 AN XY: 74294

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.803

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.952

Gnomad4 SAS AF: 0.833

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.732

Gnomad4 OTH AF: 0.778

Alfa AF: 0.745 Hom.: 24492

Bravo AF: 0.779

Asia WGS AF: 0.894 AC: 3108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.62

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: rs6416772; hg19: chr16-56819171;