Genetic Variant NM_015135.3:c.112C>T (chr7-135571188-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_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. 14/22 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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

nephrotic syndrome, type 13
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NUP205 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015135.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NUP205	NM_015135.3	MANE Select	c.112C>T	p.Leu38Phe	missense	Exon 2 of 43	NP_055950.2	Q92621
	NUP205	NM_001329434.2		c.-974C>T		5_prime_UTR	Exon 2 of 43	NP_001316363.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NUP205	ENST00000285968.11	TSL:1 MANE Select	c.112C>T	p.Leu38Phe	missense	Exon 2 of 43	ENSP00000285968.6	Q92621
NUP205	ENST00000921555.1		c.208C>T	p.Leu70Phe	missense	Exon 3 of 44	ENSP00000591614.1
NUP205	ENST00000921547.1		c.112C>T	p.Leu38Phe	missense	Exon 2 of 44	ENSP00000591606.1

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

GnomAD2 exomes

AF:

0.000124

AC:

AN:

194328

AF XY:

0.0000375

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 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

African (AFR)

AF:

0.00133

AC:

AN:

28494

American (AMR)

AF:

0.000180

AC:

AN:

33368

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23020

East Asian (EAS)

AF:

0.00

AC:

AN:

32618

South Asian (SAS)

AF:

0.0000308

AC:

AN:

64878

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48292

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5300

European-Non Finnish (NFE)

AF:

9.53e-7

AC:

AN:

1048994

Other (OTH)

AF:

0.000332

AC:

AN:

54144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000452

AC:

AN:

150500

Hom.:

Cov.:

AF XY:

0.000463

AC XY:

AN XY:

73422

show subpopulations

African (AFR)

AF:

0.00150

AC:

AN:

41218

American (AMR)

AF:

0.000200

AC:

AN:

14978

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.000208

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9836

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67758

Other (OTH)

AF:

0.000961

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.527

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000181

Hom.:

Bravo

AF:

0.000457

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000189

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

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

PhyloP100

3.9

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

Mutation Taster

=75/25

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over