17-5386713-T-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002532.6(NUP88):​c.2157A>T​(p.Lys719Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K719K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NUP88 NM_002532.6 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3159722).

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>T	p.Lys719Asn	missense	Exon 16 of 17	NP_002523.2
	NUP88	NM_001320653.2		c.2205A>T	p.Lys735Asn	missense	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>T	p.Lys719Asn	missense	Exon 16 of 17	ENSP00000458954.1	Q99567
	NUP88	ENST00000948890.1		c.2232A>T	p.Lys744Asn	missense	Exon 16 of 17	ENSP00000618949.1
	NUP88	ENST00000225696.9	TSL:5	c.2205A>T	p.Lys735Asn	missense	Exon 16 of 17	ENSP00000225696.5	J3KMX1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 6104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.013
PrimateAI	Uncertain	0.61	T
Sift4G	Uncertain	0.0050	D
Polyphen		0.049	B
Vest4		0.50
MutPred		0.59		Loss of ubiquitination at K719 (P = 0.0148)
MVP		0.50
MPC		0.48
ClinPred		0.81	D
GERP RS		3.5
Varity_R		0.12
gMVP		0.45

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

Other links and lift over

dbSNP: rs1071705; hg19: chr17-5290033;