16-56747918-C-T

Position:

• chr16-56747918-C-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.-14-316C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 174,156 control chromosomes in the GnomAD database, including 67,412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (59334 hom., cov: 31)
  • Exomes 𝑓: 0.85 (8078 hom.)
• Consequence: NUP93 NM_014669.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.320

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=-0.88).
• BP6: Variant 16-56747918-C-T is Benign according to our data. Variant chr16-56747918-C-T is described in ClinVar as [Benign]. Clinvar id is 1291690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP93	NM_014669.5	c.-14-316C>T		intron_variant		ENST00000308159.10	NP_055484.3
NUP93	XM_005256263.4	c.-50C>T		5_prime_UTR_variant	1/22		XP_005256320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP93	ENST00000308159.10	c.-14-316C>T		intron_variant		1	NM_014669.5	ENSP00000310668	P1

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133911 AN: 152124 Hom.: 59275 Cov.: 31

Gnomad AFR AF: 0.965

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.933

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.876

GnomAD4 exome AF: 0.853 AC: 18702 AN: 21914 Hom.: 8078 Cov.: 0 AF XY: 0.854 AC XY: 9680 AN XY: 11332

Gnomad4 AFR exome AF: 0.967

Gnomad4 AMR exome AF: 0.918

Gnomad4 ASJ exome AF: 0.846

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.916

Gnomad4 FIN exome AF: 0.763

Gnomad4 NFE exome AF: 0.820

Gnomad4 OTH exome AF: 0.850

GnomAD4 genome AF: 0.880 AC: 134029 AN: 152242 Hom.: 59334 Cov.: 31 AF XY: 0.883 AC XY: 65733 AN XY: 74418

Gnomad4 AFR AF: 0.965

Gnomad4 AMR AF: 0.913

Gnomad4 ASJ AF: 0.836

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.932

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.823

Gnomad4 OTH AF: 0.878

Alfa AF: 0.843 Hom.: 6757

Bravo AF: 0.893

Asia WGS AF: 0.956 AC: 3326 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.73

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: rs4783958; hg19: chr16-56781830;