rs142893035

Variant names:

• chr7-135571188-C-T
• rs142893035
• NM_015135.3:c.112C>T

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87
• Publications: 0 publications found

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

ACMG classification

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

Sel.	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: 68 AN: 150420 Hom.: 0 Cov.: 29

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: 24 AN: 194328 AF XY: 0.0000375

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: 65 AN: 1339108 Hom.: 0 Cov.: 29 AF XY: 0.0000422 AC XY: 28 AN XY: 664058

African (AFR) AF: 0.00133 AC: 38 AN: 28494

American (AMR) AF: 0.000180 AC: 6 AN: 33368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23020

East Asian (EAS) AF: 0.00 AC: 0 AN: 32618

South Asian (SAS) AF: 0.0000308 AC: 2 AN: 64878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5300

European-Non Finnish (NFE) AF: 9.53e-7 AC: 1 AN: 1048994

Other (OTH) AF: 0.000332 AC: 18 AN: 54144

GnomAD4 genome AF: 0.000452 AC: 68 AN: 150500 Hom.: 0 Cov.: 29 AF XY: 0.000463 AC XY: 34 AN XY: 73422

African (AFR) AF: 0.00150 AC: 62 AN: 41218

American (AMR) AF: 0.000200 AC: 3 AN: 14978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67758

Other (OTH) AF: 0.000961 AC: 2 AN: 2082

Alfa AF: 0.000181 Hom.: 0

Bravo AF: 0.000457

ESP6500AA AF: 0.00250 AC: 11

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000189 AC: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Benign	0.031
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.9
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.030
Sift	Benign	0.052	T
Sift4G	Benign	0.25	T
Polyphen		0.49	P
Vest4		0.30
MVP		0.33
MPC		0.36
ClinPred		0.040	T
GERP RS		3.5
Varity_R		0.060
gMVP		0.29
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs142893035; hg19: chr7-135255936;