17-5386713-T-C

Variant names:

• chr17-5386713-T-C
• rs1071705
• NM_002532.6:c.2157A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002532.6(NUP88):​c.2157A>G​(p.Lys719Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 1,594,484 control chromosomes in the GnomAD database, including 153,299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15298 hom., cov: 32)
  • Exomes 𝑓: 0.43 (138001 hom.)
• Consequence: NUP88 NM_002532.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0130

Genes affected

NUP88 (HGNC:8067): (nucleoporin 88) 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, a family of 50 to 100 proteins, are the main components of the nuclear pore complex in eukaryotic cells. The protein encoded by this gene belongs to the nucleoporin family and is associated with the oncogenic nucleoporin CAN/Nup214 in a dynamic subcomplex. This protein is also overexpressed in a large number of malignant neoplasms and precancerous dysplasias. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 17-5386713-T-C is Benign according to our data. Variant chr17-5386713-T-C is described in ClinVar as [Benign]. Clinvar id is 1327043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.013 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP88	NM_002532.6	c.2157A>G	p.Lys719Lys	synonymous_variant	Exon 16 of 17	ENST00000573584.6	NP_002523.2
NUP88	NM_001320653.2	c.2205A>G	p.Lys735Lys	synonymous_variant	Exon 16 of 17		NP_001307582.1
NUP88	XM_047436155.1	c.1812A>G	p.Lys604Lys	synonymous_variant	Exon 16 of 17		XP_047292111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP88	ENST00000573584.6	c.2157A>G	p.Lys719Lys	synonymous_variant	Exon 16 of 17	1	NM_002532.6	ENSP00000458954.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66423 AN: 151992 Hom.: 15289 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.428

GnomAD2 exomes AF: 0.477 AC: 119820 AN: 251288 AF XY: 0.481

Gnomad AFR exome AF: 0.414

Gnomad AMR exome AF: 0.431

Gnomad ASJ exome AF: 0.392

Gnomad EAS exome AF: 0.839

Gnomad FIN exome AF: 0.579

Gnomad NFE exome AF: 0.388

Gnomad OTH exome AF: 0.457

GnomAD4 exome AF: 0.425 AC: 613504 AN: 1442374 Hom.: 138001 Cov.: 29 AF XY: 0.431 AC XY: 310067 AN XY: 718948

Gnomad4 AFR exome AF: 0.405 AC: 13390 AN: 33092

Gnomad4 AMR exome AF: 0.429 AC: 19165 AN: 44694

Gnomad4 ASJ exome AF: 0.382 AC: 9920 AN: 25966

Gnomad4 EAS exome AF: 0.842 AC: 33335 AN: 39584

Gnomad4 SAS exome AF: 0.622 AC: 53401 AN: 85826

Gnomad4 FIN exome AF: 0.557 AC: 29727 AN: 53404

Gnomad4 NFE exome AF: 0.388 AC: 424856 AN: 1094358

Gnomad4 Remaining exome AF: 0.451 AC: 26936 AN: 59732

GnomAD4 genome AF: 0.437 AC: 66476 AN: 152110 Hom.: 15298 Cov.: 32 AF XY: 0.452 AC XY: 33638 AN XY: 74342

Gnomad4 AFR AF: 0.415 AC: 0.415032 AN: 0.415032

Gnomad4 AMR AF: 0.413 AC: 0.41322 AN: 0.41322

Gnomad4 ASJ AF: 0.388 AC: 0.388473 AN: 0.388473

Gnomad4 EAS AF: 0.837 AC: 0.83655 AN: 0.83655

Gnomad4 SAS AF: 0.648 AC: 0.647534 AN: 0.647534

Gnomad4 FIN AF: 0.588 AC: 0.588352 AN: 0.588352

Gnomad4 NFE AF: 0.392 AC: 0.392466 AN: 0.392466

Gnomad4 OTH AF: 0.433 AC: 0.433239 AN: 0.433239

Alfa AF: 0.397 Hom.: 6104

Bravo AF: 0.421

Asia WGS AF: 0.749 AC: 2600 AN: 3478

EpiCase AF: 0.396

EpiControl AF: 0.395

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Fetal akinesia deformation sequence 4 Benign:1

Sep 05, 2021

Genome-Nilou Lab

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	-0.67
CADD	Benign	8.4
DANN	Benign	0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1071705; hg19: chr17-5290033; COSMIC: COSV52582787; COSMIC: COSV52582787;