Variant 17-75209881-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_024844.5(NUP85):c.186T>C(p.Asp62Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0842 in 1,587,594 control chromosomes in the GnomAD database, including 6,203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.066 ( 445 hom., cov: 32)

Exomes 𝑓: 0.086 ( 5758 hom. )

Consequence

NUP85
NM_024844.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.265

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 17-75209881-T-C is Benign according to our data. Variant chr17-75209881-T-C is described in ClinVar as [Benign]. Clinvar id is 1600649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.265 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NUP85	NM_024844.5 linkuse as main transcript	c.186T>C	p.Asp62Asp	synonymous_variant	3/19	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.186T>C	p.Asp62Asp	synonymous_variant	3/19	1	NM_024844.5	ENSP00000245544.4		Q9BW27-1

Frequencies

GnomAD3 genomes

AF:

0.0663

AC:

10092

AN:

152156

Hom.:

445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0162

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.0596

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.0561

Gnomad SAS

AF:

0.0598

Gnomad FIN

AF:

0.0550

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0964

Gnomad OTH

AF:

0.0838

GnomAD3 exomes

AF:

0.0784

AC:

17637

AN:

225044

Hom.:

781

AF XY:

0.0817

AC XY:

10014

AN XY:

122620

show subpopulations

Gnomad AFR exome

AF:

0.0126

Gnomad AMR exome

AF:

0.0400

Gnomad ASJ exome

AF:

0.135

Gnomad EAS exome

AF:

0.0573

Gnomad SAS exome

AF:

0.0612

Gnomad FIN exome

AF:

0.0565

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.0884

GnomAD4 exome

AF:

0.0861

AC:

123563

AN:

1435320

Hom.:

5758

Cov.:

AF XY:

0.0860

AC XY:

61422

AN XY:

714228

show subpopulations

Gnomad4 AFR exome

AF:

0.0124

Gnomad4 AMR exome

AF:

0.0424

Gnomad4 ASJ exome

AF:

0.137

Gnomad4 EAS exome

AF:

0.0507

Gnomad4 SAS exome

AF:

0.0622

Gnomad4 FIN exome

AF:

0.0585

Gnomad4 NFE exome

AF:

0.0929

Gnomad4 OTH exome

AF:

0.0817

GnomAD4 genome

AF:

0.0662

AC:

10088

AN:

152274

Hom.:

445

Cov.:

AF XY:

0.0643

AC XY:

4787

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0161

Gnomad4 AMR

AF:

0.0595

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.0558

Gnomad4 SAS

AF:

0.0594

Gnomad4 FIN

AF:

0.0550

Gnomad4 NFE

AF:

0.0965

Gnomad4 OTH

AF:

0.0829

Alfa

AF:

0.0882

Hom.:

345

Bravo

AF:

0.0627

Asia WGS

AF:

0.0530

AC:

184

AN:

3478

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	Jan 31, 2024	- -
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

Mar 05, 2020

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

BayesDel_noAF

Benign

-0.54

CADD

Benign

7.5

DANN

Benign

0.64

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

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