rs1071705

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-5386713-T-C
• chr17-5386713-T-A
• chr17-5386713-T-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
• Publications: 29 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002532.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP88	NM_002532.6	MANE Select	c.2157A>G	p.Lys719Lys	synonymous	Exon 16 of 17	NP_002523.2
	NUP88	NM_001320653.2		c.2205A>G	p.Lys735Lys	synonymous	Exon 16 of 17	NP_001307582.1	J3KMX1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP88	ENST00000573584.6	TSL:1 MANE Select	c.2157A>G	p.Lys719Lys	synonymous	Exon 16 of 17	ENSP00000458954.1	Q99567
	NUP88	ENST00000948890.1		c.2232A>G	p.Lys744Lys	synonymous	Exon 16 of 17	ENSP00000618949.1
	NUP88	ENST00000225696.9	TSL:5	c.2205A>G	p.Lys735Lys	synonymous	Exon 16 of 17	ENSP00000225696.5	J3KMX1

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

African (AFR) AF: 0.405 AC: 13390 AN: 33092

American (AMR) AF: 0.429 AC: 19165 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 9920 AN: 25966

East Asian (EAS) AF: 0.842 AC: 33335 AN: 39584

South Asian (SAS) AF: 0.622 AC: 53401 AN: 85826

European-Finnish (FIN) AF: 0.557 AC: 29727 AN: 53404

Middle Eastern (MID) AF: 0.485 AC: 2774 AN: 5718

European-Non Finnish (NFE) AF: 0.388 AC: 424856 AN: 1094358

Other (OTH) 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

African (AFR) AF: 0.415 AC: 17218 AN: 41486

American (AMR) AF: 0.413 AC: 6314 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1348 AN: 3470

East Asian (EAS) AF: 0.837 AC: 4335 AN: 5182

South Asian (SAS) AF: 0.648 AC: 3125 AN: 4826

European-Finnish (FIN) AF: 0.588 AC: 6213 AN: 10560

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

European-Non Finnish (NFE) AF: 0.392 AC: 26683 AN: 67988

Other (OTH) AF: 0.433 AC: 915 AN: 2112

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Fetal akinesia deformation sequence 4 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.4
DANN	Benign	0.77
PhyloP100		0.013
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: rs1071705; hg19: chr17-5290033; COSMIC: COSV52582787; COSMIC: COSV52582787;