7-135557955-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015135.3(NUP205):c.11C>T(p.Pro4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00626 in 1,613,878 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0064 ( 39 hom. )

Consequence

NUP205
NM_015135.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.828

Variant links:

Genes affected

NUP205 (HGNC:18658): (nucleoporin 205) This gene encodes a nucleoporin, which is a subunit of the nuclear pore complex that functions in active transport of proteins, RNAs and ribonucleoprotein particles between the nucleus and cytoplasm. Mutations in this gene are associated with steroid-resistant nephrotic syndrome. [provided by RefSeq, Jul 2016]

NUP205 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038821697).

BP6

Variant 7-135557955-C-T is Benign according to our data. Variant chr7-135557955-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1619681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP205	NM_015135.3 link	c.11C>T	p.Pro4Leu	missense_variant	Exon 1 of 43	ENST00000285968.11	NP_055950.2	Q92621
NUP205	NM_001329434.2 link	c.-1075C>T		5_prime_UTR_variant	Exon 1 of 43		NP_001316363.2	Q92621

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP205	ENST00000285968.11 link	c.11C>T	p.Pro4Leu	missense_variant	Exon 1 of 43	1	NM_015135.3	ENSP00000285968.6		Q92621
NUP205	ENST00000489493.1 link	n.24C>T		non_coding_transcript_exon_variant	Exon 1 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.00516

AC:

786

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00550

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.00490

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00742

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00567

AC:

1427

AN:

251458

Hom.:

AF XY:

0.00595

AC XY:

809

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.000984

Gnomad AMR exome

AF:

0.00347

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00764

Gnomad FIN exome

AF:

0.00582

Gnomad NFE exome

AF:

0.00747

Gnomad OTH exome

AF:

0.00684

GnomAD4 exome

AF:

0.00638

AC:

9325

AN:

1461548

Hom.:

Cov.:

AF XY:

0.00646

AC XY:

4697

AN XY:

727102

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00329

Gnomad4 ASJ exome

AF:

0.00486

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00788

Gnomad4 FIN exome

AF:

0.00562

Gnomad4 NFE exome

AF:

0.00689

Gnomad4 OTH exome

AF:

0.00546

GnomAD4 genome

AF:

0.00515

AC:

785

AN:

152330

Hom.:

Cov.:

AF XY:

0.00554

AC XY:

413

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00549

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.00490

Gnomad4 NFE

AF:

0.00742

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00684

Hom.:

Bravo

AF:

0.00444

TwinsUK

AF:

0.0105

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00767

AC:

ExAC

AF:

0.00552

AC:

670

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00981

EpiControl

AF:

0.00830

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NUP205: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

NUP205-related disorder

Benign:1

Jul 15, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.015

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.20

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.74

REVEL

Benign

0.023

Sift

Benign

0.24

Sift4G

Benign

0.16

Polyphen

0.0

Vest4

0.15

MVP

0.082

MPC

0.23

ClinPred

0.041

GERP RS

0.57

Varity_R

0.054

gMVP

0.13

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