17-75208539-G-A

Position:

chr17-75208539-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024844.5(NUP85):c.46G>A(p.Val16Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,588,086 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00070 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 31 hom. )

Consequence

NUP85
NM_024844.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.51

Variant links:

Genes affected

NUP85 (HGNC:8734): (nucleoporin 85) This gene encodes a protein component of the Nup107-160 subunit of the nuclear pore complex. Nuclear pore complexes are embedded in the nuclear envelope and promote bidirectional transport of macromolecules between the cytoplasm and nucleus. The encoded protein can also bind to the C-terminus of chemokine (C-C motif) receptor 2 (CCR2) and promote chemotaxis of monocytes, thereby participating in the inflammatory response. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

NUP85 links:

NUP85 (HGNC:):

NUP85 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055289567).

BP6

Variant 17-75208539-G-A is Benign according to our data. Variant chr17-75208539-G-A is described in ClinVar as [Benign]. Clinvar id is 1600474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000698 (106/151880) while in subpopulation SAS AF= 0.021 (101/4814). AF 95% confidence interval is 0.0177. There are 2 homozygotes in gnomad4. There are 85 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP85	NM_024844.5 linkuse as main transcript	c.46G>A	p.Val16Met	missense_variant	2/19	ENST00000245544.9	NP_079120.1	Q9BW27-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUP85	ENST00000245544.9 linkuse as main transcript	c.46G>A	p.Val16Met	missense_variant	2/19	1	NM_024844.5	ENSP00000245544.4		Q9BW27-1

Frequencies

GnomAD3 genomes

AF:

0.000705

AC:

107

AN:

151768

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00234

AC:

588

AN:

250780

Hom.:

AF XY:

0.00318

AC XY:

431

AN XY:

135506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0189

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.00120

AC:

1723

AN:

1436206

Hom.:

Cov.:

AF XY:

0.00173

AC XY:

1238

AN XY:

716036

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000404

Gnomad4 SAS exome

AF:

0.0187

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000266

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.000698

AC:

106

AN:

151880

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0210

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00271

AC:

329

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 27, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

NUP85-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 09, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0055

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.64

N;.

REVEL

Benign

0.12

Sift

Uncertain

0.012

D;.

Sift4G

Benign

0.082

T;T

Polyphen

0.97

D;.

Vest4

0.20

MVP

0.17

MPC

0.26

ClinPred

0.047

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.056

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over