7-135571246-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001329434.2(NUP205):c.-916C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000187 in 1,387,392 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

NUP205
NM_001329434.2 5_prime_UTR_premature_start_codon_gain

Scores

Splicing: ADA: 0.04098

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.80

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUP205	NM_015135.3 link	c.170C>T	p.Pro57Leu	missense_variant, splice_region_variant	Exon 2 of 43	ENST00000285968.11	NP_055950.2	Q92621
NUP205	NM_001329434.2 link	c.-916C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 43		NP_001316363.2	Q92621
NUP205	NM_001329434.2 link	c.-916C>T		splice_region_variant	Exon 2 of 43		NP_001316363.2	Q92621
NUP205	NM_001329434.2 link	c.-916C>T		5_prime_UTR_variant	Exon 2 of 43		NP_001316363.2	Q92621

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUP205	ENST00000285968.11 link	c.170C>T	p.Pro57Leu	missense_variant, splice_region_variant	Exon 2 of 43	1	NM_015135.3	ENSP00000285968.6		Q92621
NUP205	ENST00000489493.1 link	n.425C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149466

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000670

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000572

AC:

AN:

157260

Hom.:

AF XY:

0.0000569

AC XY:

AN XY:

87914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000736

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000194

AC:

AN:

1237926

Hom.:

Cov.:

AF XY:

0.0000132

AC XY:

AN XY:

604356

show subpopulations

Gnomad4 AFR exome

AF:

0.0000395

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000517

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000147

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000141

Gnomad4 OTH exome

AF:

0.0000203

GnomAD4 genome

AF:

0.0000134

AC:

AN:

149466

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72836

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000670

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Nov 27, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 57 of the NUP205 protein (p.Pro57Leu). This variant is present in population databases (rs369458508, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with NUP205-related conditions. ClinVar contains an entry for this variant (Variation ID: 1449439). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.19

MetaRNN

Uncertain

0.69

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-8.0

REVEL

Benign

0.26

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.010

Polyphen

0.99

Vest4

0.62

MVP

0.56

MPC

0.74

ClinPred

0.94

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.71

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.041

dbscSNV1_RF

Benign

0.19

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