Genetic Variant NM_015135.3:c.153C>T (chr7-135571229-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7

The NM_015135.3(NUP205):c.153C>T(p.Ile51Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000347 in 1,394,598 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00046 ( 1 hom., cov: 29)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

NUP205
NM_015135.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.12

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: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 7-135571229-C-T is Benign according to our data. Variant chr7-135571229-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2057170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.12 with no splicing effect.

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.153C>T	p.Ile51Ile	synonymous	Exon 2 of 43	NP_055950.2	Q92621
	NUP205	NM_001329434.2		c.-933C>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.153C>T	p.Ile51Ile	synonymous	Exon 2 of 43	ENSP00000285968.6	Q92621
NUP205	ENST00000921555.1		c.249C>T	p.Ile83Ile	synonymous	Exon 3 of 44	ENSP00000591614.1
NUP205	ENST00000921547.1		c.153C>T	p.Ile51Ile	synonymous	Exon 2 of 44	ENSP00000591606.1

Frequencies

GnomAD3 genomes

AF:

0.000457

AC:

AN:

148870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000739

Gnomad AMI

AF:

0.0187

Gnomad AMR

AF:

0.000743

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00129

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000296

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000292

AC:

AN:

160848

AF XY:

0.000323

show subpopulations

Gnomad AFR exome

AF:

0.0000960

Gnomad AMR exome

AF:

0.000650

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000576

Gnomad NFE exome

AF:

0.000324

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000334

AC:

416

AN:

1245676

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

213

AN XY:

610030

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25666

American (AMR)

AF:

0.000529

AC:

AN:

20798

Ashkenazi Jewish (ASJ)

AF:

0.000254

AC:

AN:

19692

East Asian (EAS)

AF:

0.00

AC:

AN:

31236

South Asian (SAS)

AF:

0.00

AC:

AN:

47116

European-Finnish (FIN)

AF:

0.000644

AC:

AN:

45018

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4934

European-Non Finnish (NFE)

AF:

0.000351

AC:

352

AN:

1001524

Other (OTH)

AF:

0.000382

AC:

AN:

49692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000457

AC:

AN:

148922

Hom.:

Cov.:

AF XY:

0.000442

AC XY:

AN XY:

72448

show subpopulations

African (AFR)

AF:

0.0000738

AC:

AN:

40656

American (AMR)

AF:

0.000742

AC:

AN:

14834

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5106

South Asian (SAS)

AF:

0.00

AC:

AN:

4756

European-Finnish (FIN)

AF:

0.00129

AC:

AN:

9272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000296

AC:

AN:

67598

Other (OTH)

AF:

0.00

AC:

AN:

2042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.000403

Hom.:

Bravo

AF:

0.000484

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

NUP205-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

1.1

Mutation Taster

=98/2

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

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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