16-56798390-C-T

Variant names:

• chr16-56798390-C-T
• rs9927884
• NM_014669.5:c.298-86C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014669.5(NUP93):​c.298-86C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,090,826 control chromosomes in the GnomAD database, including 8,256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1385 hom., cov: 32)
  • Exomes 𝑓: 0.12 (6871 hom.)
• Consequence: NUP93 NM_014669.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.53

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-56798390-C-T is Benign according to our data. Variant chr16-56798390-C-T is described in ClinVar as [Benign]. Clinvar id is 1233605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP93	NM_014669.5	c.298-86C>T		intron_variant	Intron 3 of 21	ENST00000308159.10	NP_055484.3
NUP93	NM_001242795.2	c.-72-86C>T		intron_variant	Intron 1 of 19		NP_001229724.1
NUP93	NM_001242796.2	c.-72-86C>T		intron_variant	Intron 1 of 19		NP_001229725.1
NUP93	XM_005256263.4	c.298-86C>T		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.298-86C>T		intron_variant	Intron 3 of 21	1	NM_014669.5	ENSP00000310668.5

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19805 AN: 152020 Hom.: 1384 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0953

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.116 AC: 108937 AN: 938688 Hom.: 6871 AF XY: 0.118 AC XY: 57457 AN XY: 485764

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.0749

Gnomad4 ASJ exome AF: 0.0636

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.0971

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.130 AC: 19821 AN: 152138 Hom.: 1385 Cov.: 32 AF XY: 0.130 AC XY: 9665 AN XY: 74380

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0680

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0953

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.127

Alfa AF: 0.117 Hom.: 1869

Bravo AF: 0.131

Asia WGS AF: 0.152 AC: 530 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0080
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9927884; hg19: chr16-56832302; COSMIC: COSV57429555;