Variant 7-135571188-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015135.3(NUP205):c.112C>T(p.Leu38Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000893 in 1,489,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

NUP205
NM_015135.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.87

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02476409).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NUP205	NM_015135.3 linkuse as main transcript	c.112C>T	p.Leu38Phe	missense_variant	2/43	ENST00000285968.11
NUP205	NM_001329434.2 linkuse as main transcript	c.-974C>T		5_prime_UTR_variant	2/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NUP205	ENST00000285968.11 linkuse as main transcript	c.112C>T	p.Leu38Phe	missense_variant	2/43	1	NM_015135.3	P1
NUP205	ENST00000489493.1 linkuse as main transcript	n.367C>T		non_coding_transcript_exon_variant	2/3	4

Frequencies

GnomAD3 genomes

AF:

0.000452

AC:

AN:

150420

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00151

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000201

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000969

GnomAD3 exomes

AF:

0.000124

AC:

AN:

194328

Hom.:

AF XY:

0.0000375

AC XY:

AN XY:

106680

show subpopulations

Gnomad AFR exome

AF:

0.00186

Gnomad AMR exome

AF:

0.0000441

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000875

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000485

AC:

AN:

1339108

Hom.:

Cov.:

AF XY:

0.0000422

AC XY:

AN XY:

664058

show subpopulations

Gnomad4 AFR exome

AF:

0.00133

Gnomad4 AMR exome

AF:

0.000180

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000308

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.53e-7

Gnomad4 OTH exome

AF:

0.000332

GnomAD4 genome

AF:

0.000452

AC:

AN:

150500

Hom.:

Cov.:

AF XY:

0.000463

AC XY:

AN XY:

73422

show subpopulations

Gnomad4 AFR

AF:

0.00150

Gnomad4 AMR

AF:

0.000200

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000961

Alfa

AF:

0.000118

Hom.:

Bravo

AF:

0.000457

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000189

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Sep 29, 2022

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NUP205 protein function. This variant has not been reported in the literature in individuals affected with NUP205-related conditions. This variant is present in population databases (rs142893035, gnomAD 0.2%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 38 of the NUP205 protein (p.Leu38Phe). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

Eigen

Benign

0.031

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.023

MetaRNN

Benign

0.025

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.45

REVEL

Benign

0.030

Sift

Benign

0.052

Sift4G

Benign

0.25

Polyphen

0.49

Vest4

0.30

MVP

0.33

MPC

0.36

ClinPred

0.040

GERP RS

3.5

Varity_R

0.060

gMVP

0.29

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