17-5387504-C-A

Variant names:

• chr17-5387504-C-A
• rs748486
• NM_002532.6:c.1836-38G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002532.6(NUP88):​c.1836-38G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,603,424 control chromosomes in the GnomAD database, including 154,282 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15265 hom., cov: 32)
  • Exomes 𝑓: 0.43 (139017 hom.)
• Consequence: NUP88 NM_002532.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0890
• Publications: 17 publications found

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]

NUP88 Gene-Disease associations (from GenCC):

• fetal akinesia deformation sequence 4

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• fetal akinesia deformation sequence 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 17-5387504-C-A is Benign according to our data. Variant chr17-5387504-C-A is described in ClinVar as Benign. ClinVar VariationId is 1327049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP88	NM_002532.6	c.1836-38G>T		intron_variant	Intron 13 of 16	ENST00000573584.6	NP_002523.2
NUP88	NM_001320653.2	c.1884-38G>T		intron_variant	Intron 13 of 16		NP_001307582.1
NUP88	XM_047436155.1	c.1491-38G>T		intron_variant	Intron 13 of 16		XP_047292111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP88	ENST00000573584.6	c.1836-38G>T		intron_variant	Intron 13 of 16	1	NM_002532.6	ENSP00000458954.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66354 AN: 151934 Hom.: 15256 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.427

GnomAD2 exomes AF: 0.477 AC: 119567 AN: 250766 AF XY: 0.481

Gnomad AFR exome AF: 0.413

Gnomad AMR exome AF: 0.430

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: 0.458

GnomAD4 exome AF: 0.426 AC: 618544 AN: 1451372 Hom.: 139017 Cov.: 29 AF XY: 0.432 AC XY: 312251 AN XY: 722730

African (AFR) AF: 0.405 AC: 13464 AN: 33272

American (AMR) AF: 0.429 AC: 19165 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 9982 AN: 26064

East Asian (EAS) AF: 0.842 AC: 33384 AN: 39644

South Asian (SAS) AF: 0.622 AC: 53531 AN: 86026

European-Finnish (FIN) AF: 0.556 AC: 29709 AN: 53398

Middle Eastern (MID) AF: 0.486 AC: 2794 AN: 5750

European-Non Finnish (NFE) AF: 0.389 AC: 429395 AN: 1102446

Other (OTH) AF: 0.452 AC: 27120 AN: 60062

GnomAD4 genome AF: 0.437 AC: 66407 AN: 152052 Hom.: 15265 Cov.: 32 AF XY: 0.452 AC XY: 33616 AN XY: 74338

African (AFR) AF: 0.415 AC: 17187 AN: 41458

American (AMR) AF: 0.413 AC: 6319 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 1349 AN: 3472

East Asian (EAS) AF: 0.837 AC: 4328 AN: 5172

South Asian (SAS) AF: 0.647 AC: 3121 AN: 4826

European-Finnish (FIN) AF: 0.587 AC: 6214 AN: 10578

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26652 AN: 67948

Other (OTH) AF: 0.433 AC: 913 AN: 2110

Alfa AF: 0.346 Hom.: 1913

Bravo AF: 0.421

Asia WGS AF: 0.749 AC: 2599 AN: 3478

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	-0.88
CADD	Benign	2.1
DANN	Benign	0.56
PhyloP100		-0.089
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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

Other links and lift over

dbSNP: rs748486; hg19: chr17-5290824; COSMIC: COSV52582788; COSMIC: COSV52582788;